{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T11:38:23Z","timestamp":1772451503817,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T00:00:00Z","timestamp":1694304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","doi-asserted-by":"publisher","award":["2022.06464.PTDC"],"award-info":[{"award-number":["2022.06464.PTDC"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","doi-asserted-by":"publisher","award":["2020.04935.BD"],"award-info":[{"award-number":["2020.04935.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tetracyclines (TCs) are a class of broad-spectrum antibiotics with diverse pharmacotherapeutic properties due to their various functional groups being attached to a common core structure. Beyond their antibacterial activity, TCs trigger pleiotropic effects on eukaryotic cells, including anti-inflammatory and potentially osteogenic capabilities. Consequently, TCs hold promise for repurposing in various clinical applications, including bone-related conditions. This study presents the first comprehensive comparison of the in vitro osteogenic potential of four TCs\u2014tetracycline, doxycycline, minocycline, and sarecycline, within human mesenchymal stem cells. Cultures were characterized for metabolic activity, cell morphology and cytoskeleton organization, osteogenic gene expression, alkaline phosphatase (ALP) activity, and the activation of relevant signaling pathways. TCs stimulated actin remodeling processes, inducing morphological shifts consistent with osteogenic differentiation. Osteogenic gene expression and ALP activity supported the osteoinduction by TCs, demonstrating significant increases in ALP levels and the upregulation of RUNX2, SP7, and SPARC genes. Minocycline and sarecycline exhibited the most potent osteogenic induction, comparable to conventional osteogenic inducers. Signaling pathway analysis revealed that tetracycline and doxycycline activate the Wnt pathway, while minocycline and sarecycline upregulated Hedgehog signaling. Overall, the present findings suggest that TCs promote osteogenic differentiation through distinct pathways, making them promising candidates for targeted therapy in specific bone-related disorders.<\/jats:p>","DOI":"10.3390\/cells12182244","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T09:05:17Z","timestamp":1694423117000},"page":"2244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Unveiling the Osteogenic Potential of Tetracyclines: A Comparative Study in Human Mesenchymal Stem Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6910-1705","authenticated-orcid":false,"given":"Victor","family":"Martin","sequence":"first","affiliation":[{"name":"BoneLab\u2014Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, University of Porto, 4050-453 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-5892","authenticated-orcid":false,"given":"Ana Francisca","family":"Bettencourt","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8567-0032","authenticated-orcid":false,"given":"Catarina","family":"Santos","sequence":"additional","affiliation":[{"name":"CQE Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"},{"name":"EST Set\u00fabal, CDP2T, Instituto Polit\u00e9cnico de Set\u00fabal, 2910-761 Set\u00fabal, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9391-9574","authenticated-orcid":false,"given":"Maria Helena","family":"Fernandes","sequence":"additional","affiliation":[{"name":"BoneLab\u2014Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, University of Porto, 4050-453 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-2123","authenticated-orcid":false,"given":"Pedro Sousa","family":"Gomes","sequence":"additional","affiliation":[{"name":"BoneLab\u2014Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, University of Porto, 4050-453 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kim, Y.Y.-H.Y., Kim, J., Lee, H., Shin, W.-R., Lee, S., Lee, J., Park, J.-I., Jhun, B.H., Kim, Y.Y.-H.Y., and Yi, S.-J. (2019). Tetracycline Analogs Inhibit Osteoclast Differentiation by Suppressing MMP-9-Mediated Histone H3 Cleavage. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20164038"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1080\/07853890.2022.2085881","article-title":"Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance","volume":"54","author":"LaPlante","year":"2022","journal-title":"Ann. Med."},{"key":"ref_3","unstructured":"Nelson, M.L., and Ismail, M.Y. (2007). Comprehensive Medicinal Chemistry II, Elsevier."},{"key":"ref_4","unstructured":"Bryskier, A. (2014). Antimicrobial Agents, ASM Press."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1515\/hsz-2013-0292","article-title":"Tetracycline antibiotics and resistance mechanisms","volume":"395","author":"Nguyen","year":"2014","journal-title":"Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/antibiotics1010001","article-title":"Classification Framework and Chemical Biology of Tetracycline-Structure-Based Drugs","volume":"1","author":"Fuoco","year":"2012","journal-title":"Antibiotics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"642822","DOI":"10.3389\/fphar.2021.642822","article-title":"Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives","volume":"12","author":"Alqarni","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/bph.12139","article-title":"Minocycline: Far beyond an antibiotic","volume":"169","author":"Zarzuelo","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.biopha.2017.07.078","article-title":"Minocycline attenuates the development of diabetic neuropathy by inhibiting spinal cord Notch signaling in rat","volume":"94","author":"Yang","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bunick, C.G., Keri, J., Tanaka, S.K., Furey, N., Damiani, G., Johnson, J.L., and Grada, A. (2021). Antibacterial mechanisms and efficacy of sarecycline in animal models of infection and inflammation. Antibiotics, 10.","DOI":"10.3390\/antibiotics10040439"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/idj.12221","article-title":"Non-antibacterial tetracycline formulations: Host-modulators in the treatment of periodontitis and relevant systemic diseases","volume":"66","author":"Golub","year":"2016","journal-title":"Int. Dent. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbrc.2015.09.140","article-title":"Therapeutic effects of antibiotic drug tigecycline against cervical squamous cell carcinoma by inhibiting Wnt\/\u03b2-catenin signaling","volume":"467","author":"Li","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"40667","DOI":"10.18632\/oncotarget.5842","article-title":"Doxycycline reverses epithelial-to-mesenchymal transition and suppresses the proliferation and metastasis of lung cancer cells","volume":"6","author":"Qin","year":"2015","journal-title":"Oncotarget"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"714366","DOI":"10.3389\/fcimb.2021.714366","article-title":"Tetracycline, an Appropriate Reagent for Measuring Bone-Formation Activity in the Murine Model of the Streptococcus mutans-Induced Bone Loss","volume":"11","author":"Hirohashi","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1089\/ten.tec.2017.0400","article-title":"Live Quantitative Monitoring of Mineral Deposition in Stem Cells Using Tetracycline Hydrochloride","volume":"24","author":"Ahmed","year":"2018","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121832","DOI":"10.1016\/j.ijpharm.2022.121832","article-title":"Poly(DL-lactic acid) scaffolds as a bone targeting platform for the co-delivery of antimicrobial agents against S. aureus-C.albicans mixed biofilms","volume":"622","author":"Zegre","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118821","DOI":"10.1016\/j.ijpharm.2019.118821","article-title":"Understanding intracellular trafficking and anti-inflammatory effects of minocycline chitosan-nanoparticles in human gingival fibroblasts for periodontal disease treatment","volume":"572","author":"Martin","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"35009","DOI":"10.1088\/1748-605X\/aa68b8","article-title":"Minocycline-releasing PMMA system as a space maintainer for staged bone reconstructions\u2014In vitro antibacterial, cytocompatibility and anti-inflammatory characterization","volume":"12","author":"Silva","year":"2017","journal-title":"Biomed. Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1177\/0885328218795290","article-title":"In vivo tissue response and antibacterial efficacy of minocycline delivery system based on polymethylmethacrylate bone cement","volume":"33","author":"Silva","year":"2018","journal-title":"J. Biomater. Appl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"015006","DOI":"10.1088\/1758-5090\/7\/1\/015006","article-title":"Metal ion-assisted self-assembly of complexes for controlled and sustained release of minocycline for biomedical applications","volume":"7","author":"Zhang","year":"2015","journal-title":"Biofabrication"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1902\/jop.2009.080574","article-title":"The effect of doxycycline hyclate, chlorhexidine gluconate, and minocycline hydrochloride on osteoblastic proliferation and differentiation in vitro","volume":"80","author":"Almazin","year":"2009","journal-title":"J. Periodontol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1902\/jop.1993.64.8s.819","article-title":"Blocking Periodontal Disease Progression by Inhibiting Tissue-Destructive Enzymes: A Potential Therapeutic Role for Tetracyclines and Their Chemically-Modified Analogs","volume":"64","author":"Rifkin","year":"1993","journal-title":"J. Periodontol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S8756-3282(00)00297-0","article-title":"Tetracyclines induce apoptosis in osteoclasts","volume":"27","author":"Bettany","year":"2000","journal-title":"Bone"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s00223-009-9328-5","article-title":"Tetracyclines Inhibit Rat Osteoclast Formation and Activity In Vitro and Affect Bone Turnover in Young Rats In Vivo","volume":"86","author":"Zhou","year":"2010","journal-title":"Calcif. Tissue Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.4049\/jimmunol.1101174","article-title":"Tetracyclines Convert the Osteoclastic-Differentiation Pathway of Progenitor Cells To Produce Dendritic Cell-like Cells","volume":"188","author":"Kinugawa","year":"2012","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.archoralbio.2006.10.005","article-title":"Effect of therapeutic levels of doxycycline and minocycline in the proliferation and differentiation of human bone marrow osteoblastic cells","volume":"52","author":"Gomes","year":"2007","journal-title":"Arch. Oral Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.actbio.2007.12.006","article-title":"Cell-induced response by tetracyclines on human bone marrow colonized hydroxyapatite and Bonelike\u00ae","volume":"4","author":"Gomes","year":"2008","journal-title":"Acta Biomater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/jac\/dkl224","article-title":"Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines","volume":"58","author":"Agwuh","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1749-6632.2011.06354.x","article-title":"The history of the tetracyclines","volume":"1241","author":"Nelson","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_30","first-page":"45","article-title":"Sarecycline and the Narrow-Spectrum Tetracycline Concept: Currently Available Data and Potential Clinical Relevance in Dermatology","volume":"13","year":"2020","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.phrs.2010.10.007","article-title":"Clinical applications of non-antimicrobial tetracyclines in dermatology","volume":"63","author":"Monk","year":"2011","journal-title":"Pharmacol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.phrs.2010.12.003","article-title":"Clinical studies on the management of periodontal diseases utilizing subantimicrobial dose doxycycline (SDD)","volume":"63","author":"Caton","year":"2011","journal-title":"Pharmacol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00774-023-01428-9","article-title":"Repurposing sarecycline for osteoinductive therapies: An in vitro and ex vivo assessment","volume":"41","author":"Martin","year":"2023","journal-title":"J. Bone Miner. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s13287-018-0914-1","article-title":"Adipose-derived and bone marrow mesenchymal stem cells: A donor-matched comparison","volume":"9","author":"Fristad","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1186\/s13287-017-0716-x","article-title":"Tissue source determines the differentiation potentials of mesenchymal stem cells: A comparative study of human mesenchymal stem cells from bone marrow and adipose tissue","volume":"8","author":"Xu","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/scrt328","article-title":"Effects of dexamethasone, ascorbic acid and \u03b2-glycerophosphate on the osteogenic differentiation of stem cells in vitro","volume":"4","author":"Langenbach","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/S0142-9612(99)00192-1","article-title":"Human bone cell cultures in biocompatibility testing. Part II: Effect of ascorbic acid, \u03b2-glycerophosphate and dexamethasone on osteoblastic differentiation","volume":"21","author":"Coelho","year":"2000","journal-title":"Biomaterials"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s12079-021-00635-1","article-title":"Signaling network regulating osteogenesis in mesenchymal stem cells","volume":"16","author":"Thomas","year":"2022","journal-title":"J. Cell Commun. Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"C539","DOI":"10.1152\/ajpcell.00047.2010","article-title":"Tetracyclines: A pleitropic family of compounds with promising therapeutic properties. Review of the literature","volume":"299","author":"Griffin","year":"2010","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.phrs.2010.10.004","article-title":"Tetracycline compounds with non-antimicrobial organ protective properties: Possible mechanisms of action","volume":"63","author":"Griffin","year":"2011","journal-title":"Pharmacol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1177\/08959374980120010901","article-title":"Tetracycline Derivatives Induce Apoptosis Selectively in Cultured Monocytes and Macrophages but not in Mesenchymal Cells","volume":"12","author":"Bettany","year":"1998","journal-title":"Adv. Dent. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/(SICI)1097-4644(19990915)74:4<616::AID-JCB11>3.0.CO;2-Q","article-title":"Kinetics of osteoprogenitor proliferation and osteoblast differentiation in vitro","volume":"74","author":"Malaval","year":"1999","journal-title":"J. Cell. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/jcb.10174","article-title":"Real-time quantitative RT-PCR analysis of human bone marrow stromal cells during osteogenic differentiation in vitro","volume":"85","author":"Frank","year":"2002","journal-title":"J. Cell. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.mce.2003.06.002","article-title":"Cell lines and primary cell cultures in the study of bone cell biology","volume":"228","author":"Kartsogiannis","year":"2004","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Song, H., Fares, M., Maguire, K.R., Sid\u00e9n, \u00c5., and Pot\u00e1cov\u00e1, Z. (2014). Cytotoxic Effects of Tetracycline Analogues (Doxycycline, Minocycline and COL-3) in Acute Myeloid Leukemia HL-60 Cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114457"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6640","DOI":"10.1038\/s41598-017-06794-9","article-title":"Engineering the geometrical shape of mesenchymal stromal cells through defined cyclic stretch regimens","volume":"7","author":"Walters","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1002\/jcb.20234","article-title":"Cytoskeletal organization of human mesenchymal stem cells (MSC) changes during their osteogenic differentiation","volume":"93","author":"Cambiazo","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"R52","DOI":"10.1186\/gb-2014-15-3-r52","article-title":"Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis","volume":"15","author":"Wu","year":"2014","journal-title":"Genome Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s11914-023-00778-7","article-title":"SP7: From Bone Development to Skeletal Disease","volume":"21","author":"Wang","year":"2023","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.matbio.2016.02.001","article-title":"SPARC\/osteonectin in mineralized tissue","volume":"52\u201354","author":"Rosset","year":"2016","journal-title":"Matrix Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Komori, T. (2022). Whole Aspect of Runx2 Functions in Skeletal Development. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105776"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ballhause, T.M., Jiang, S., Baranowsky, A., Brandt, S., Mertens, P.R., Frosch, K.-H., Yorgan, T., and Keller, J. (2021). Relevance of Notch Signaling for Bone Metabolism and Regeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031325"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.ajpath.2019.05.005","article-title":"Notch Signaling in Osteogenesis, Osteoclastogenesis, and Angiogenesis","volume":"189","author":"Luo","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/jor.20954","article-title":"Axin2 regulates chondrocyte maturation and axial skeletal development","volume":"28","author":"Dao","year":"2009","journal-title":"J. Orthop. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.1242\/dev.081679","article-title":"Twist1 mediates repression of chondrogenesis by \u03b2-catenin to promote cranial bone progenitor specification","volume":"139","author":"Goodnough","year":"2012","journal-title":"Development"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"46","DOI":"10.22203\/eCM.v024a04","article-title":"The importance of WNT pathways for bone metabolism and their regulation by implant topography","volume":"24","author":"Galli","year":"2012","journal-title":"Eur. Cells Mater."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"110975","DOI":"10.1016\/j.mce.2020.110975","article-title":"Doxycycline restores the impaired osteogenic commitment of diabetic-derived bone marrow mesenchymal stromal cells by increasing the canonical WNT signaling","volume":"518","author":"Gomes","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/ijos.2017.28","article-title":"Doxycycline induces bone repair and changes in Wnt signalling","volume":"9","author":"Gomes","year":"2017","journal-title":"Int. J. Oral Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/jor.22562","article-title":"Activation of hedgehog signaling during fracture repair enhances osteoblastic-dependent matrix formation","volume":"32","author":"Baht","year":"2014","journal-title":"J. Orthop. Res."},{"key":"ref_60","first-page":"169","article-title":"[Hedgehog signaling pathway and osteoporosis]","volume":"27","author":"Luo","year":"2014","journal-title":"Zhongguo Gu Shang"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1002\/jcp.24823","article-title":"Novel Hedgehog Agonists Promote Osteoblast Differentiation in Mesenchymal Stem Cells","volume":"230","author":"Nakamura","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kwon, Y., Park, C., Lee, J., Park, D.H., Jeong, S., Yun, C.-H., Park, O.-J., and Han, S.H. (2021). Regulation of Bone Cell Differentiation and Activation by Microbe-Associated Molecular Patterns. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115805"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1002\/jbmr.133","article-title":"Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation","volume":"25","author":"Chen","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"7487","DOI":"10.1007\/s12035-018-0933-z","article-title":"Regulatory Effects of Neuroinflammatory Responses Through Brain-Derived Neurotrophic Factor Signaling in Microglial Cells","volume":"55","author":"Lai","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1177\/1060028018818094","article-title":"Omadacycline: A New Tetracycline Antibiotic","volume":"53","author":"Dougherty","year":"2019","journal-title":"Ann. Pharmacother."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Rusu, A., and Buta, E.L. (2021). The Development of Third-Generation Tetracycline Antibiotics and New Perspectives. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122085"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2244\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:48:12Z","timestamp":1760129292000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,10]]},"references-count":66,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cells12182244"],"URL":"https:\/\/doi.org\/10.3390\/cells12182244","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,10]]}}}