{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:52:59Z","timestamp":1793692379272,"version":"4.5.1"},"reference-count":194,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) can be defined as the result of pathological processes of various etiologies leading to damage to the articular structures. Although the mechanism of degenerative changes has become better understood due to the plethora of biochemical and genetic studies, the drug that could stop the degenerative cascade is still unknown. All available forms of OA therapy are based on symptomatic treatment. According to actual guidelines, comprehensive treatment of OA should always include a combination of various therapeutic options aimed at common goals, which are pain relief in the first place, and then the improvement of function. Local treatment has become more common practice, which takes place between rehabilitation and pharmacological treatment in the hierarchy of procedures. Only in the case of no improvement and the presence of advanced lesions visible in imaging tests, should surgery be considered. Currently, an increasing number of studies are being published suggesting that intra-articular injections may be as effective or even more effective than non-steroidal anti-inflammatory drugs (NSAIDs) and result in fewer systemic adverse events. The most commonly used preparations are hyaluronic acid (HA), glucocorticosteroids (GS), and also platelet-rich plasma (PRP) in recent years. This review aims to present the mechanism of action and clinical effectiveness of different pharmacological options in relieving pain and improving functions in OA as well as the emerging approach in intra-articular treatment with PRP.<\/jats:p>","DOI":"10.3390\/ijms23031566","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T23:02:06Z","timestamp":1643497326000},"page":"1566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Overview of First-Line and Second-Line Pharmacotherapies for Osteoarthritis with Special Focus on Intra-Articular Treatment"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4945-2369","authenticated-orcid":false,"given":"Alicja","family":"Nowaczyk","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, LudwikRydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 2 dr. A. Jurasza St., 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-0626","authenticated-orcid":false,"given":"Dawid","family":"Szwedowski","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Trauma Surgery, Provincial Polyclinical Hospital, 87-100 Toru\u0144, Poland"},{"name":"Orthopedic Arthroscopic Surgery International (O.A.S.I.) Bioresearch Foundation, Gobbi N.P.O., 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2744-8342","authenticated-orcid":false,"given":"Ignacio","family":"Dallo","sequence":"additional","affiliation":[{"name":"Unit of Biological Therapies, SportMe Medical Center, Department of Orthopaedic Surgery and Sports Medicine, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4521-8065","authenticated-orcid":false,"given":"Jacek","family":"Nowaczyk","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry and Physicochemistry of Polymers, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarina St., 87-100 Toru\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"ref_1","unstructured":"(2022, January 10). International Classification of Diseases. Available online: https:\/\/www.icd10data.com\/ICD10CM\/Codes\/M00-M99\/M05-M14\/M06-\/M06.9."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/art.41142","article-title":"2019 American College of Rheumatology\/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee","volume":"72","author":"Kolasinski","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_3","first-page":"75","article-title":"Rheumatoid arthritis and the concept of autoimmune disease","volume":"14","author":"Neidhart","year":"2019","journal-title":"Int. J. Clin. Rheumatol."},{"key":"ref_4","unstructured":"(2022, January 10). International Classification of Diseases. Available online: https:\/\/www.icd10data.com\/ICD10CM\/Codes\/M00-M99\/M15-M19."},{"key":"ref_5","first-page":"e101","article-title":"Osteoarthritis: New perspectives","volume":"1","author":"Gabay","year":"2012","journal-title":"J. Spine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.joca.2013.07.017","article-title":"Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: A review","volume":"21","author":"Zhu","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1080\/08977194.2018.1548444","article-title":"Growth factor signalling in osteoarthritis","volume":"36","author":"Huang","year":"2018","journal-title":"Growth Factors"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Szwedowski, D., Szczepanek, J., Paczesny, \u0141., P\u0119ka\u0142a, P., Zabrzy\u0144ski, J., and Kruczy\u0144ski, J. (2020). Genetics in Cartilage Lesions: Basic Science and Therapy Approaches. IJMS, 21.","DOI":"10.3390\/ijms21155430"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1146\/annurev-neuro-072116-031121","article-title":"Nerve growth factor and pain mechanisms","volume":"40","author":"Denk","year":"2017","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/ar2463","article-title":"Nitric oxide in inflammation and pain associated with osteoarthritis","volume":"10","author":"Abramson","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/BOR.0000000000000162","article-title":"The biological basis of osteoarthritis: State of the evidence","volume":"27","author":"Malemud","year":"2015","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.11005\/jbm.2018.25.2.65","article-title":"Differential role of transforming growth factor-beta in an osteoarthritic or a healthy joint","volume":"25","year":"2018","journal-title":"J. Bone Metab."},{"key":"ref_13","first-page":"1037","article-title":"Management of common musculoskeletal problems: Survey of Ontario primary care physicians","volume":"158","author":"Glazier","year":"1998","journal-title":"CMAJ"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1179544120946743","article-title":"Expert Opinion on the Extensive Use of Prescription Crystalline Glucosamine Sulfate in the Multimodal Treatment of Osteoarthritis in Ukraine, Kazakhstan, Uzbekistan, and Armenia","volume":"13","author":"Gnylorybov","year":"2020","journal-title":"Clin. Med. Insights Arthritis Musculoskelet. Disord."},{"key":"ref_15","unstructured":"Rasheed Kayani, R., Shamim, R., Sultana Munir, S., Sultana, M., Nazir, S.U.R., Riaz, H., Nazir, T., Maaz Ali, M., and Islam, A. (Altern. Ther. Health Med., 2021). Medicinal Plants and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Treatment of Arthritis: A Literature Review, Altern. Ther. Health Med., online ahead of print."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.5435\/JAAOSGlobal-D-20-00046","article-title":"Which Nonsurgical Treatments Do Patients Believe Are Most Effective for Hip and Knee Arthritis?","volume":"4","author":"Nahhas","year":"2020","journal-title":"JAAOS Glob. Res. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sun, Y., Zuo, Z., and Kuang, Y. (2020). An emerging target in the battle against osteoarthritis: Macrophage polarization. IJMS, 21.","DOI":"10.3390\/ijms21228513"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.4049\/jimmunol.0803007","article-title":"The mechanism of osteoclast differentiation induced by IL-1","volume":"183","author":"Kim","year":"2009","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nri2691","article-title":"The IL-1 family: Regulators of immunity","volume":"10","author":"Sims","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sims, N.A., and Lorenzo, J.A. (2020). Local regulators of bone: Interleukin-1, tumor necrosis factor, interferons, the IL-6 family, and additional cytokines. Principles of Bone Biology, Elsevier.","DOI":"10.1016\/B978-0-12-814841-9.00050-6"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"bvaa112","DOI":"10.1210\/jendso\/bvaa112","article-title":"The Role of Interleukin-6 in Bone","volume":"4","author":"Lorenzo","year":"2020","journal-title":"J. Endocr. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s00296-012-2375-7","article-title":"Relation of interleukin-6 in rheumatoid arthritis patients to systemic bone loss and structural bone damage","volume":"33","author":"Meguid","year":"2013","journal-title":"Rheumatol. Int."},{"key":"ref_23","first-page":"4","article-title":"Nerve growth factor in the psychiatric brain","volume":"55","author":"Ferraguti","year":"2020","journal-title":"Riv. Psichiatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41584-020-00528-4","article-title":"The evolution of nerve growth factor inhibition in clinical medicin","volume":"17","author":"Wise","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/09537104.2020.1849605","article-title":"PRP in wound healing applications","volume":"32","author":"Oneto","year":"2021","journal-title":"Platelets"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105207","DOI":"10.1016\/j.jbspin.2021.105207","article-title":"Physical activity for osteoarthritis: Efficiency and review of recommandations","volume":"88","author":"Daste","year":"2021","journal-title":"Jt. Bone Spine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.2106\/00004623-201310160-00010","article-title":"The American Academy of Orthopaedic Surgeons Evidence-Based Guideline on: Treatment of Osteoarthritis of the Knee, 2nd Edition","volume":"95","author":"Jevsevar","year":"2013","journal-title":"JBJS"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e434","DOI":"10.5435\/JAAOS-D-18-00351","article-title":"Management of osteoarthritis of the hip: Evidence-based clinical practice guideline","volume":"26","author":"Quinn","year":"2017","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarth. Cartil."},{"key":"ref_30","first-page":"797","article-title":"EULAR recommendations for the health professional\u2019s approach to pain management in inflammatory arthritis and osteoarthritis","volume":"77","author":"Geenen","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","unstructured":"(2022, January 10). Anatomical Therapeutic Chemical Classification System. Available online: https:\/\/www.whocc.no\/atc_ddd_index\/?code=M&showdescription=no."},{"key":"ref_32","unstructured":"(2022, January 10). Anatomical Therapeutic Chemical Classification System. Available online: https:\/\/www.atccode.com\/M02A."},{"key":"ref_33","unstructured":"(2022, January 10). Anatomical Therapeutic Chemical Classification System. Available online: https:\/\/www.atccode.com\/M02AA."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.cca.2020.11.003","article-title":"Traditional and modern management strategies for rheumatoid arthritis","volume":"512","author":"Akram","year":"2021","journal-title":"Clin. Chim. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s00296-020-04526-3","article-title":"Drug interactions in the treatment of rheumatoid arthritis and psoriatic arthritis","volume":"40","author":"Pflugbeil","year":"2020","journal-title":"Rheumatol. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrd1109","article-title":"Therapeutic strategies for rheumatoid arthritis","volume":"2","author":"Smolen","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_37","unstructured":"(2022, January 10). Anatomical Therapeutic Chemical Classification System. Available online: https:\/\/www.atccode.com\/N02BE."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e00835","DOI":"10.1002\/prp2.835","article-title":"Pharmacological hypotheses: Is acetaminophen selective in its cyclooxygenase inhibition?","volume":"9","author":"Esh","year":"2021","journal-title":"Pharm. Res. Perspect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4181","DOI":"10.1021\/acs.molpharmaceut.9b00508","article-title":"Paracetamol\u2013Galactose Conjugate: A Novel Prodrug for an Old Analgesic Drug","volume":"16","author":"Sodano","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_40","unstructured":"(2022, January 10). Anatomical Therapeutic Chemical Classification System. Available online: https:\/\/www.atccode.com\/N02BA."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1002\/1521-3773(20001016)39:20<3601::AID-ANIE3601>3.0.CO;2-R","article-title":"Hydrogen bonding interactions in amorphous salicyl salicylate","volume":"39","author":"Greener","year":"2000","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_42","unstructured":"(2022, January 10). WebMD Health Corp. Available online: https:\/\/www.webmd.com\/drugs\/2\/drug-8704\/salsalate-oral\/details."},{"key":"ref_43","unstructured":"Drug Index A to, Z. (2022, January 10). Available online: https:\/\/www.drugs.com\/mtm\/salsalate.html."},{"key":"ref_44","first-page":"80","article-title":"Salsalate: Its role in the management of rheumatic disease","volume":"3","author":"Singleton","year":"1980","journal-title":"Clin. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"114358","DOI":"10.1016\/j.molliq.2020.114358","article-title":"Ultrasonic-assisted efficient synthesis of inclusion complexes of salsalate drug and \u03b2-cyclodextrin derivatives for potent biomedical applications","volume":"319","author":"Mohandoss","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"L3","DOI":"10.1152\/ajplung.2001.280.1.L3","article-title":"Effect of acetylsalicylic acid on endogenous I\u03baB kinase activity in lung epithelial cells","volume":"280","author":"Yoo","year":"2001","journal-title":"Am. J. Physiol. Lung C"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Yeasmin, F., and Choi, H.W. (2020). Natural Salicylates and Their Roles in Human Health. IJMS, 21.","DOI":"10.3390\/ijms21239049"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(02)01828-9","article-title":"Anti-Inflammatory effects of aspirin and sodium salicylate","volume":"447","author":"Amann","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s40266-019-00662-z","article-title":"Safety of symptomatic slow-acting drugs for osteoarthritis: Outcomes of a systematic review and meta-analysis","volume":"36","author":"Honvo","year":"2019","journal-title":"Drugs Aging"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1172\/JCI200113418","article-title":"Cyclooxygenase-Selective inhibition of prostanoid formation: Transducing biochemical selectivity into clinical read-outs","volume":"108","author":"Patrono","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_51","first-page":"CD009865","article-title":"Celecoxib for osteoarthritis","volume":"5","author":"Puljak","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_52","first-page":"1","article-title":"Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: Network meta-analysis","volume":"375","author":"Pereira","year":"2021","journal-title":"BMJ"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s40744-020-00196-6","article-title":"Topical diclofenac, an efficacious treatment for osteoarthritis: A narrative review","volume":"7","author":"Revel","year":"2020","journal-title":"Rheumatol. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1001\/jama.2020.22171","article-title":"Diagnosis and Treatment of Hip and Knee Osteoarthritis","volume":"325","author":"Katz","year":"2021","journal-title":"JAMA"},{"key":"ref_55","unstructured":"(2022, January 10). Anatomical Therapeutic Chemical Classification System. Available online: https:\/\/www.whocc.no\/atc_ddd_index\/?code=M01AC&showdescription=no."},{"key":"ref_56","first-page":"556","article-title":"Mid-Term effects of meloxicam on collagen type II degradation in a rat osteoarthritis model induced by iodoacetate","volume":"63","author":"Csifo","year":"2015","journal-title":"Farmacia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1016\/j.joca.2013.09.005","article-title":"Intra-Articular injection of the selective cyclooxygenase-2 inhibitor meloxicam (Mobic) reduces experimental osteoarthritis and nociception in rats","volume":"21","author":"Wen","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1185\/03007995.2015.1112772","article-title":"Efficacy and safety of low-dose SoluMatrix meloxicam in the treatment of osteoarthritis pain: A 12-week, phase 3 study","volume":"31","author":"Altman","year":"2015","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_59","unstructured":"(2022, January 10). Anatomical Therapeutic Chemical Classification System. Available online: https:\/\/www.atccode.com\/N02."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"147","DOI":"10.4081\/or.2018.7782","article-title":"Pharmacological treatment of knee osteoarthritis: Special considerations of the new German guideline","volume":"10","author":"Steinmeyer","year":"2018","journal-title":"Orthop. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"108","DOI":"10.2174\/1573397113666170829155149","article-title":"Current treatment options for osteoarthritis","volume":"14","author":"Hermann","year":"2018","journal-title":"Curr. Rheumatol. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.bcp.2019.02.034","article-title":"Emerging therapeutic agents in osteoarthritis","volume":"165","author":"Alcaraz","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00223-020-00672-9","article-title":"Prospects for therapies in osteoarthritis","volume":"109","author":"Ghouri","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1136\/annrheumdis-2020-219181","article-title":"Long-Term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study","volume":"80","author":"Eckstein","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.2147\/DDDT.S295224","article-title":"The development of disease-modifying therapies for osteoarthritis (DMOADs): The evidence to date","volume":"15","author":"Oo","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"110594","DOI":"10.1016\/j.biopha.2020.110594","article-title":"Diacerein: Recent insight into pharmacological activities and molecular pathways","volume":"131","author":"Almezgagi","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/ddr.21232","article-title":"Combination of diacerhein and antiepileptic drugs after local peripheral, and oral administration in the rat formalin test","volume":"75","year":"2014","journal-title":"Drug Develop. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.pbb.2012.06.018","article-title":"Diacerein decreases visceral pain through inhibition of glutamatergic neurotransmission and cytokine signaling in mice","volume":"102","author":"Gadotti","year":"2012","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1111\/1756-185X.12741","article-title":"Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord","volume":"20","author":"Calixto","year":"2017","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-016-0652-1","article-title":"Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5\/ERK pathway in the trigeminal ganglion of mice","volume":"13","author":"Zhang","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.phrs.2014.10.008","article-title":"Diacerein is a potent and selective inhibitor of palmitoylethanolamide inactivation with analgesic activity in a rat model of acute inflammatory pain","volume":"91","author":"Petrosino","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8127","DOI":"10.1007\/s00018-021-03983-8","article-title":"Pharmaceutical therapeutics for articular regeneration and restoration: State-of-the-Art technology for screening small molecular drugs","volume":"78","author":"Chen","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.freeradbiomed.2019.09.024","article-title":"Quercetin alleviates rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages","volume":"145","author":"Hu","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1083\/jcb.201103167","article-title":"Generating a Wnt switch: It\u2019s all about the right dosage","volume":"193","author":"Kestler","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Novicky, A., Caetano-Silva, S.P., Javaheri, B., and Pitsillides, A.A. (2018). The Mechanics of Skeletal Development. Developmental Biology and Musculoskeletal Tissue Engineering, Academic Press.","DOI":"10.1016\/B978-0-12-811467-4.00002-4"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41584-020-00533-7","article-title":"Mechanisms and therapeutic implications of cellular senescence in osteoarthritis","volume":"17","author":"Coryell","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1759720X211006959","DOI":"10.1177\/1759720X211006959","article-title":"Promising targets for therapy of osteoarthritis: A review on the Wnt and TGF-\u03b2 signalling pathways","volume":"13","author":"Cherifi","year":"2021","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1055\/s-0038-1676803","article-title":"Results of a phase II study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-\u03b21","volume":"33","author":"Lee","year":"2020","journal-title":"J. Knee Surg."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.exer.2016.04.007","article-title":"Crosstalk between TGF\u03b2 and Wnt signaling pathways in the human trabecular meshwork","volume":"148","author":"Webber","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.semarthrit.2021.03.005","article-title":"The Effects of sprifermin on symptoms and structure in a subgroup at risk of progression in the FORWARD knee osteoarthritis trial","volume":"51","author":"Guehring","year":"2021","journal-title":"Semin. Arthrittis Rheum."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1002\/art.41315","article-title":"Lorecivivint, a Novel Intraarticular CDC-like Kinase 2 and Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor and Wnt Pathway Modulator for the Treatment of Knee Osteoarthritis: A Phase II Randomized Trial","volume":"72","author":"Yazici","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1080\/13543784.2020.1842357","article-title":"Lorecivivint, an intra-articular potential disease-modifying osteoarthritis drug","volume":"29","author":"Sabha","year":"2020","journal-title":"Expert Opin. Investig. Drug."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/ar3436","article-title":"Desperately looking for the right target in osteoarthritis: The anti-IL-1 strategy","volume":"13","author":"Chevalier","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1136\/annrheumdis-2018-213336","article-title":"Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1\u03b1 and anti-interleukin-1\u03b2 dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis","volume":"78","author":"Kloppenburg","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/art.40840","article-title":"A Phase II Trial of Lutikizumab, an Anti\u2013Interleukin-1\u03b1\/\u03b2 Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients with Synovitis","volume":"71","author":"Fleischmann","year":"2019","journal-title":"Arthrit. Rheumatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1136\/annrheumdis-2020-218547","article-title":"Efficacy of tocilizumab in patients with hand osteoarthritis: Double blind, randomised, placebo-controlled, multicentre trial","volume":"80","author":"Richette","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/art.24096","article-title":"Intraarticular injection of anakinra in osteoarthritis of the knee: A multicenter, randomized, double-blind, placebo-controlled study","volume":"61","author":"Chevalier","year":"2009","journal-title":"Arthrit. Care Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.joca.2018.02.899","article-title":"A randomised double-blind placebo-controlled crossover trial of HUMira (adalimumab) for erosive hand OsteoaRthritis\u2013the HUMOR trial","volume":"26","author":"Aitken","year":"2018","journal-title":"Osteoarthr. Cartil."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1136\/annrheumdis-2018-213202","article-title":"Etanercept in patients with inflammatory hand osteoarthritis (EHOA): A multicentre, randomised, double-blind, placebo-controlled trial","volume":"77","author":"Kloppenburg","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_90","first-page":"135","article-title":"Disease modification in osteoarthritis: Are we there yet?","volume":"37","author":"Oo","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrrheum.2010.178","article-title":"Pharmacologic therapy for osteoarthritis\u2014The era of disease modification","volume":"7","author":"Hunter","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.joca.2012.09.017","article-title":"Equivalence of a single dose (1200 mg) compared to a three-time a day dose (400 mg) of chondroitin 4&6 sulfate in patients with knee osteoarthritis. Results of a randomized double blind placebo controlled study","volume":"21","author":"Zegels","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/art.39819","article-title":"Combined treatment with chondroitin sulfate and glucosamine sulfate shows no superiority over placebo for reduction of joint pain and functional impairment in patients with knee osteoarthritis: A six-month multicenter, randomized, double-blind, placebo-controlled clinical trial","volume":"69","author":"Largo","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.joca.2014.01.003","article-title":"OARSI guidelines for the non-surgical management of knee osteoarthritis","volume":"22","author":"McAlindon","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_95","first-page":"241","article-title":"Intra-Articular steroid injections for painful knees. Systematic review with meta-analysis","volume":"50","author":"Godwin","year":"2004","journal-title":"Can. Fam. Physician"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1136\/bmj.38039.573970.7C","article-title":"Corticosteroid injections for osteoarthritis of the knee: Meta-Analysis","volume":"328","author":"Arroll","year":"2004","journal-title":"BJM"},{"key":"ref_97","first-page":"CD005321","article-title":"Viscosupplementation for the treatment of osteoarthritis of the knee","volume":"2","author":"Bellamy","year":"2006","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/00001433-200002000-00012","article-title":"Intra-Articular corticosteroid treatment in osteoarthritis","volume":"11","author":"Creamer","year":"2000","journal-title":"Curr. Opin. Orthop."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s10067-009-1135-x","article-title":"Systemic effects of intra-articular corticosteroids","volume":"28","author":"Habib","year":"2009","journal-title":"Clin. Rheumatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1136\/ard.2008.089722","article-title":"Increased blood glucose levels following intra-articular injection of methylprednisolone acetate in patients with controlled diabetes and symptomatic osteoarthritis of the knee","volume":"67","author":"Habib","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_101","first-page":"773","article-title":"Corticosteroid treatment induces chondrocyte apoptosis in an experimental arthritis model and in chondrocyte cultures","volume":"20","author":"Nakazawa","year":"2002","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2325967115581163","DOI":"10.1177\/2325967115581163","article-title":"The effect of intra-articular corticosteroids on articular cartilage: A systematic review","volume":"3","author":"Wernecke","year":"2015","journal-title":"Orthop. J. Sports Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.arth.2019.11.017","article-title":"Risk of Periprosthetic infection following intra-articular corticosteroid injections after total knee arthroplasty","volume":"35","author":"Roecker","year":"2020","journal-title":"J. Arthroplast."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.knee.2013.07.003","article-title":"Systematic review: The safety of intra-articular corticosteroid injection prior to total knee arthroplasty","volume":"21","author":"Marsland","year":"2014","journal-title":"Knee"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11999-016-4757-8","article-title":"The John N. Insall Award: Do intraarticular injections increase the risk of infection after TKA?","volume":"475","author":"Bedard","year":"2017","journal-title":"Clin. Orthop. Relat. R."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1016\/j.arth.2015.05.027","article-title":"Does timing of previous intra-articular steroid injection affect the post-operative rate of infection in total knee arthroplasty?","volume":"30","author":"Cancienne","year":"2015","journal-title":"J. Arthroplast."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1177\/0363546508326984","article-title":"Hyaluronic acid viscosupplementation and osteoarthritis: Current uses and future directions","volume":"37","author":"Strauss","year":"2009","journal-title":"Am. J. Sports Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"538","DOI":"10.2106\/00004623-200403000-00012","article-title":"Therapeutic effects of hyaluronic acid on osteoarthritis of the knee: A meta-analysis of randomized controlled trials","volume":"86","author":"Wang","year":"2004","journal-title":"JBJS"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"10401047","DOI":"10.1056\/NEJMct1215534","article-title":"Viscosupplementation for osteoarthritis of the knee","volume":"372","author":"Hunter","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/00008505-200110000-00002","article-title":"Platelet-Rich plasma (PRP): What is PRP and what is not PRP?","volume":"10","author":"Marx","year":"2001","journal-title":"Implant Dent."},{"key":"ref_111","first-page":"2040622319825567","article-title":"Platelet-Rich plasma in osteoarthritis treatment: Review of current evidence","volume":"10","author":"Magalhaes","year":"2019","journal-title":"Ther. Adv. Chronic. Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/micr.22105","article-title":"Effect of platelet rich plasma and platelet rich fibrin on sciatic nerve regeneration in a rat model","volume":"33","author":"Lichtenfels","year":"2013","journal-title":"Microsurgery"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"147e","DOI":"10.1097\/01.prs.0000239606.92676.cf","article-title":"Platelet-rich plasma: A review of biology and applications in plastic surgery","volume":"118","author":"Eppley","year":"2006","journal-title":"Plast. Reconst. Surg."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1111\/jocd.14326","article-title":"History of autologous platelet-rich plasma: A short review","volume":"20","author":"Przylipiak","year":"2021","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/jbm.b.30886","article-title":"Effectiveness of autologous preparation rich in growth factors for the treatment of chronic cutaneous ulcers","volume":"84","author":"Anitua","year":"2008","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_116","first-page":"529","article-title":"Plasma rich in growth factors: Preliminary results of use in the preparation of future sites for implants","volume":"14","author":"Anitua","year":"1999","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"364S","DOI":"10.1177\/1947603520931170","article-title":"PRP injections for the treatment of knee osteoarthritis: A meta-analysis of randomized controlled trials","volume":"13","author":"Filardo","year":"2021","journal-title":"Cartilage"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1111\/1756-185X.13315","article-title":"Clinical outcomes are associated with changes in ultrasonographic structural appearance after platelet-rich plasma treatment for knee osteoarthritis","volume":"21","author":"Ahmad","year":"2018","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/dvdy.24463","article-title":"Vascular Endothelial Growth Factor Control Mechanisms in Skeletal Growth and Repair","volume":"246","author":"Hu","year":"2017","journal-title":"Dev. Dynam."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"FSO231","DOI":"10.4155\/fsoa-2017-0045","article-title":"An overview of platelet products (PRP, PRGF, PRF, etc.) in the Iranian studies","volume":"3","author":"Raeissadat","year":"2017","journal-title":"Future Sci. OA"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.phrs.2018.01.021","article-title":"The role of small molecule platelet-derived growth factor receptor (PDGFR) inhibitors in the treatment of neoplastic disorders","volume":"129","author":"Roskoski","year":"2018","journal-title":"Pharm. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrrheum.2016.219","article-title":"The changing role of TGF\u03b2 in healthy, ageing and osteoarthritic joints","volume":"13","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_123","first-page":"1","article-title":"Vascular endothelial growth factor in cartilage development and osteoarthritis","volume":"7","author":"Nagao","year":"2017","journal-title":"Sci. Rep. UK"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2014.01.011","article-title":"Epidermal growth factor, from gene organization to bedside","volume":"28","author":"Zeng","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3109\/09537104.2014.881991","article-title":"Platelet-Rich plasma (PRP): Methodological aspects and clinical applications","volume":"26","author":"Marques","year":"2015","journal-title":"Platelets"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"T115","DOI":"10.1530\/JME-17-0298","article-title":"40 YEARS OF IGF1: Insulin-Like growth factors: Actions on the skeleton","volume":"61","author":"Yakar","year":"2018","journal-title":"J. Mol. Endocrinol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1440-1746.2010.06549.x","article-title":"Hepatocyte growth factor twenty years on: Much more than a growth factor","volume":"26","author":"Nakamura","year":"2011","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.cyto.2016.12.025","article-title":"Hepatocyte growth factor in physiology and infectious diseases","volume":"98","author":"Imamura","year":"2017","journal-title":"Cytokine"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/nrd3599","article-title":"Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets","volume":"10","author":"Jun","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"115548","DOI":"10.1016\/j.bone.2020.115548","article-title":"Discovery of Bone Morphogenetic Proteins\u2014A Historical Perspective","volume":"140","author":"Sampath","year":"2020","journal-title":"Bone"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1445-2197.2007.04175.x","article-title":"Bone morphogenetic proteins in clinical applications","volume":"77","author":"Gautschi","year":"2007","journal-title":"ANZ J. Surg."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1161\/ATVBAHA.108.179556","article-title":"History of discovery: Platelet-Derived growth factor","volume":"31","author":"Raines","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/bdrc.10030","article-title":"Biology of platelet-derived growth factors in development","volume":"69","author":"Betsholtz","year":"2003","journal-title":"Birth Defects Res. Part C Embryo Today Rev."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1152\/physrev.2003.83.3.835","article-title":"Regulation of wound healing by growth factors and cytokines","volume":"83","author":"Werner","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1089\/ten.teb.2019.0292","article-title":"Platelet-Rich Plasma Therapy in the Treatment of Diseases Associated with Orthopedic Injuries","volume":"26","author":"Fang","year":"2020","journal-title":"Tissue Eng. Part A"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.pmr.2016.06.002","article-title":"Platelet-Rich plasma","volume":"27","author":"Peter","year":"2016","journal-title":"Phys. Med. Rehabil. Clin."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"27113","DOI":"10.1021\/acsomega.0c02543","article-title":"Preparation and Evaluation of Sustained Release Platelet-Rich Plasma-Loaded Gelatin Microspheres Using an Emulsion Method","volume":"5","author":"Yang","year":"2020","journal-title":"ACS Omega"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000084848","article-title":"Human endometrial leukemia inhibitory factor and interleukin-6: Control of secretion by transforming growth factor-\u03b2-related members","volume":"12","author":"Dubois","year":"2005","journal-title":"Neuroimmunomodulation"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Szwedowski, D., Szczepanek, J., Paczesny, \u0141., Zabrzy\u0144ski, J., Gagat, M., Mobasheri, A., and Jeka, S. (2021). The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis. IJMS, 22.","DOI":"10.3390\/ijms22115492"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5483\/BMBRep.2005.38.1.001","article-title":"Transforming growth factor-\u03b2: Biology and clinical relevance","volume":"38","author":"YiKim","year":"2005","journal-title":"BMB Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.joca.2007.09.003","article-title":"The potential role of vascular endothelial growth factor (VEGF) in cartilage: How the angiogenic factor could be involved in the pathogenesis of osteoarthritis?","volume":"16","author":"Murata","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.bone.2016.06.013","article-title":"The roles of vascular endothelial growth factor in bone repair and regeneration","volume":"91","author":"Hu","year":"2016","journal-title":"Bone"},{"key":"ref_143","first-page":"3950","article-title":"Vascular endothelial growth factor (VEGF)\u2014Key factor in normal and pathological angiogenesis","volume":"59","author":"Melincovici","year":"2018","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.jds.2021.08.011","article-title":"Tumor necrosis factor-\u03b1 enhances the expression of vascular endothelial growth factor in a mouse orthodontic tooth movement model","volume":"17","author":"Noguchi","year":"2021","journal-title":"J. Den. Sci."},{"key":"ref_145","first-page":"120082","article-title":"EGFR targeting for cancer therapy: Pharmacology and immunoconjugates with drugs and nanoparticles","volume":"592","author":"Nogueira","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1002\/sctm.17-0039","article-title":"Acceleration of fracture healing by overexpression of basic fibroblast growth factor in the mesenchymal stromal cells","volume":"6","author":"Zhang","year":"2017","journal-title":"Stem Cell. Transl. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"135","DOI":"10.5603\/JTM.2020.0004","article-title":"Autologous platelet-rich plasma therapy\u2014A promising method for tissue repair\/\/regeneration in many medical fields","volume":"13","author":"Piszczorowicz","year":"2020","journal-title":"J. Transfus. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ghir.2015.09.004","article-title":"Regulation of skeletal growth and mineral acquisition by the GH\/IGF-1 axis: Lessons from mouse models","volume":"28","author":"Yakar","year":"2016","journal-title":"Growth Horm. IGF Res."},{"key":"ref_149","first-page":"9","article-title":"Hepatocyte growth factor overexpression promotes osteoclastogenesis and exacerbates bone loss in CIA mice","volume":"27","author":"Huang","year":"2021","journal-title":"J. Orthop. Transl."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"100387","DOI":"10.1016\/j.jbo.2021.100387","article-title":"Sensory nerves: A driver of the vicious cycle in bone metastasis?","volume":"30","author":"Yoneda","year":"2021","journal-title":"J. Bone Oncol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.3389\/fcell.2020.593269","article-title":"Connective tissue growth factor: From molecular understandings to drug discovery","volume":"8","author":"Chen","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12079-013-0204-8","article-title":"CCN2: A master regulator of the genesis of bone and cartilage","volume":"7","author":"Takigawa","year":"2013","journal-title":"J. Cell Commun. Signal."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1359\/JBMR.040322","article-title":"Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor)","volume":"19","author":"Nishida","year":"2004","journal-title":"J. Bone Min. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"a021899","DOI":"10.1101\/cshperspect.a021899","article-title":"Bone morphogenetic proteins","volume":"8","author":"Katagiri","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00402-012-1641-1","article-title":"Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes","volume":"133","author":"Malhotra","year":"2013","journal-title":"Arch. Orthop. Traum. Su."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.theriogenology.2020.01.076","article-title":"Insights into nerve growth factor-\u03b2 role in bovine reproduction-Review","volume":"150","author":"Lima","year":"2020","journal-title":"Theriogenology"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"416","DOI":"10.5603\/FM.a2018.0006","article-title":"Tendon\u2014Function-related structure, simple healing process and mysterious ageing","volume":"77","author":"Grzanka","year":"2018","journal-title":"Folia Morphol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Szwedowski, D., Jaworski, \u0141., Szwedowska, W., P\u0119kala, P., and Gagat, M. (2021). Neovascularization in Meniscus and Tendon Pathology as a Potential Mechanism in Regenerative Therapies: Special Reference to Platelet-Rich Plasma Treatment. Appl. Sci., 11.","DOI":"10.3390\/app11188310"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1007\/s00167-012-2172-6","article-title":"Neovascularization in Achilles tendinopathy: Have we been chasing a red herring?","volume":"20","author":"Tol","year":"2012","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.aca.2014.10.009","article-title":"Bioanalytical chemistry of cytokines\u2014A review","volume":"853","author":"Stenken","year":"2015","journal-title":"Anal. Chim. Act."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.jaci.2010.11.050","article-title":"Interleukins, from 1 to 37, and interferon-\u03b3: Receptors, functions, and roles in diseases","volume":"127","author":"Akdis","year":"2011","journal-title":"J. Allergy Clin. Iimmunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"701","DOI":"10.3389\/fphar.2021.645842","article-title":"New Trends in Pharmacological Treatments for Osteoarthritis","volume":"12","author":"Cai","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_163","unstructured":"Vaillant, A.A.J., and Qurie, A. (2020). Interleukin. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz, J., Akhavan, N.S., Mullins, A.P., and Arjmandi, B.H. (2020). Macrophage polarization and osteoporosis: A review. Nutrients, 12.","DOI":"10.3390\/nu12102999"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1002\/jbm.a.37142","article-title":"Interleukin-4 repairs wear particle induced osteolysis by modulating macrophage polarization and bone turnover","volume":"109","author":"Pajarinen","year":"2021","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1302\/2046-3758.107.BJR-2020-0334.R4","article-title":"3D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis","volume":"10","author":"Zhao","year":"2021","journal-title":"Bone Jt. Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.3389\/fimmu.2021.708186","article-title":"Macrophages: The Good, the Bad, and the Gluttony","volume":"12","author":"Ross","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.bone.2017.04.006","article-title":"Molecular bases of the crosstalk between bone and muscle","volume":"115","author":"Karsenty","year":"2018","journal-title":"Bone"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"788","DOI":"10.3389\/fendo.2018.00788","article-title":"Interleukin-6 interweaves the bone marrow microenvironment, bone loss, and multiple myeloma","volume":"9","author":"Harmer","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0192-0561(94)00088-6","article-title":"Interleukin-8 and the chemokine family","volume":"17","author":"Baggiolini","year":"1995","journal-title":"Int. J. Immunopharmacol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.bbrc.2017.03.150","article-title":"Interferon induces interleukin 8 and bone marrow stromal cell antigen 2 expression, inhibiting the production of hepatitis B virus surface antigen from human hepatocytes","volume":"486","author":"Haga","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s00167-016-3981-9","article-title":"Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration","volume":"26","author":"Cassano","year":"2018","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3389\/fendo.2018.00313","article-title":"Role of tumor-derived chemokines in osteolytic bone metastasis","volume":"9","author":"Coniglio","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1161\/CIRCULATIONAHA.117.027889","article-title":"Interleukin-10 inhibits bone marrow fibroblast progenitor cell\u2013mediated cardiac fibrosis in pressure-overloaded myocardium","volume":"136","author":"Verma","year":"2017","journal-title":"Circulation"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1002\/jcp.29141","article-title":"Loss of interleukin-10 exacerbates early Type-1 diabetes-induced bone loss","volume":"235","author":"Dagenais","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.humpath.2017.01.007","article-title":"Transforming growth factor \u03b2\u2013and interleukin 13\u2013producing mast cells are associated with fibrosis in bone marrow","volume":"62","author":"Nakayama","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3389\/fendo.2019.00285","article-title":"The role of osteocytes in inflammatory bone loss","volume":"10","author":"Metzger","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.4110\/in.2020.20.e50","article-title":"Interleukin-10-Producing B Cells Help Suppress Ovariectomy-Mediated Osteoporosis","volume":"20","author":"Wang","year":"2020","journal-title":"Immune Netw."},{"key":"ref_179","first-page":"1","article-title":"The Application Value of Interleukin-10 and Interleukin-15 in Osteoporosis","volume":"8","author":"Lei","year":"2021","journal-title":"Open Access Libr. J."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"5757","DOI":"10.1158\/1078-0432.CCR-18-0472","article-title":"Functions and mechanisms of tumor necrosis factor-\u03b1 and noncoding RNAs in bone-invasive pituitary adenomas","volume":"24","author":"Zhu","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12979-020-00177-x","article-title":"\u201cInflammaging\u201d and bone in the OsteoLaus cohort","volume":"17","author":"Fischer","year":"2020","journal-title":"Immun. Ageing"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jpsychores.2018.05.008","article-title":"Interleukin, tumor necrosis factor-\u03b1 and C-reactive protein profiles in melancholic and non-melancholic depression: A systematic review","volume":"111","author":"Yang","year":"2018","journal-title":"J. Psychosom. Res."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1097\/JSA.0b013e3182999740","article-title":"Platelet-Rich plasma for articular cartilage repair","volume":"21","author":"Abrams","year":"2013","journal-title":"Sports Med. Arthrosc."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.joca.2007.06.006","article-title":"Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-\u03baBp65-specific siRNA","volume":"16","author":"Chen","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.jconrel.2012.02.008","article-title":"Platelet-Rich plasma loaded hydrogel scaffold enhances chondrogenic differentiation and maturation with up-regulation of CB1 and CB2","volume":"159","author":"Lee","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.joca.2012.09.018","article-title":"The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair","volume":"21","author":"Mifune","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jcot.2018.10.005","article-title":"Improvising PRP for use in osteoarthritis knee-upcoming trends and futuristic view","volume":"10","author":"Dhillon","year":"2019","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1177\/0363546512466383","article-title":"The systemic effects of platelet-rich plasma injection","volume":"41","author":"Wasterlain","year":"2013","journal-title":"Am. J. Sports Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"e1773","DOI":"10.1016\/j.eats.2020.07.023","article-title":"Osteo-Core Plasty: A Minimally Invasive Approach for Subchondral Bone Marrow Lesions of the Knee","volume":"9","author":"Szwedowski","year":"2020","journal-title":"Arthrosc. Tech."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"298","DOI":"10.2106\/JBJS.K.00154","article-title":"Efficacy of autologous platelet-rich plasma use for orthopaedic indications: A meta-analysis","volume":"94","author":"Sheth","year":"2012","journal-title":"JBJS"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1089\/scd.2021.0053","article-title":"Prospective Study Comparing Leukocyte-Poor Platelet-Rich Plasma Combined with Hyaluronic Acid and Autologous Microfragmented Adipose Tissue in Patients with Early Knee Osteoarthritis","volume":"30","author":"Dallo","year":"2021","journal-title":"Stem Cells Dev."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.arthro.2020.11.052","article-title":"Platelet-Rich plasma combined with hyaluronic acid improves pain and function compared with hyaluronic acid alone in knee osteoarthritis: A systematic review and meta-analysis","volume":"37","author":"Karasavvidis","year":"2021","journal-title":"Arthrosc. J. Arthrosc. Relat. Surg."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1177\/0963689719880527","article-title":"Autologous micro-fragmented adipose tissue as stem cell-based natural scaffold for cartilage defect repair","volume":"28","author":"Xu","year":"2019","journal-title":"Cell Transplant."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s40634-018-0169-x","article-title":"Autologous micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis: An update at 3 year follow-up","volume":"5","author":"Russo","year":"2018","journal-title":"J. Exp. Orthop."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1566\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:10:44Z","timestamp":1760134244000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,29]]},"references-count":194,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23031566"],"URL":"https:\/\/doi.org\/10.3390\/ijms23031566","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,29]]}}}