{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:33:24Z","timestamp":1788269604685,"version":"build-2803163510"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005626","name":"Universit\u00e4t Regensburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005626","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>About 655\u00a0million persons worldwide are affected by osteoarthritis (OA). As no therapy modifies disease progression long-term, there is an immense clinical need for novel therapies. The joints are innervated by alpha calcitonin gene-related peptide (\u03b1CGRP)- and substance P (SP)-positive sensory nerve fibers. Both neuropeptides have trophic effects on target cells within the joints. The aim of this study was to examine the effects of SP- and \u03b1CGRP-expressing intra-articular (i.a.) applied rat(r)BMSC on cartilage and subchondral bone structural changes after OA induction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Mice were subjected to destabilization of the medial meniscus (DMM) surgery, followed by i.a. injections with rBMSC, transduced with lacZ, SP or \u03b1CGRP. 2, 8 and 16 weeks after DMM\/Sham surgery, motion analysis and serum marker analysis were performed. Cartilage and subchondral bone properties were assessed by OA scoring, atomic force microscopy and nano-CT analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>OARSI scores of the medial cartilage compartments indicated induction and progression of OA after DMM surgery in all groups. Differences between the treatment groups were mostly restricted to the lateral cartilage compartments, where \u03b1CGRP caused a decrease of structural changes. DMM-rBMSC-\u03b1CGRP or -SP mice displayed decreased cartilage stiffness in the cartilage middle zone. DMM-rBMSC-\u03b1CGRP mice revealed improved mobility, whereas Sham-rBMSC-SP mice revealed reduced mobility compared to rBMSC-lacZ. With respect to condyle length, subarticular bone and ephiphyseal bone morphology, DMM-rBMSC-SP mice had more alterations indicating either a more progressed OA stage or a more severe OA pathology compared to controls. In addition, DMM-rBMSC-SP mice developed osteophytes already 8 weeks after surgery. Adiponectin serum level was increased in DMM-rBMSC-\u03b1CGRP mice, and MIP1b level in DMM-rBMSC-SP mice. Notably, pain and inflammation markers increased over time in rBMSC-SP mice while rBMSC-\u03b1CGRP mice revealed a bell-shaped curve with a peak at 8 weeks.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We conclude that i.a. injection of rBMSC in general have a beneficial effect on cartilage matrix structure, subchondral bone microarchitecture and inflammation. rBMSC-\u03b1CGRP have anabolic and possible analgesic properties and may attenuate the progression or severity of OA. In contrast, rBMSC-SP exert a more catabolic influence on knee joints of both, Sham and DMM mice, making it a potential candidate for inhibition studies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13287-025-04155-2","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T14:18:28Z","timestamp":1741184308000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of intra-articular applied rat BMSCs expressing alpha-calcitonin gene-related peptide or substance P on osteoarthritis pathogenesis in a murine surgical osteoarthritis model"],"prefix":"10.1186","volume":"16","author":[{"given":"Sabine","family":"St\u00f6ckl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahed","family":"Taheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Asid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Toelge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hauke","family":"Clausen-Schaumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Schilling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2549-8285","authenticated-orcid":false,"given":"Susanne","family":"Gr\u00e4ssel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"issue":"10182","key":"4155_CR1","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","volume":"393","author":"DJ Hunter","year":"2019","unstructured":"Hunter DJ, Bierma-Zeinstra S. Osteoarthr Lancet. 2019;393(10182):1745\u201359.","journal-title":"Osteoarthr Lancet"},{"issue":"6","key":"4155_CR2","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1002\/art.34453","volume":"64","author":"RF Loeser","year":"2012","unstructured":"Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64(6):1697\u2013707.","journal-title":"Arthritis Rheum"},{"issue":"7","key":"4155_CR3","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1136\/annrheumdis-2013-204763","volume":"73","author":"M Cross","year":"2014","unstructured":"Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323\u201330.","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"4155_CR4","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1177\/19476035231157335","volume":"14","author":"DR Diduch","year":"2023","unstructured":"Diduch DR, Crawford DC, Ranawat AS, Victor J, Flanigan DC. Implantable shock Absorber provides Superior Pain Relief and functional improvement compared with high tibial osteotomy in patients with mild-to-moderate medial knee osteoarthritis: a 2-Year report. Cartilage. 2023;14(2):152\u201363.","journal-title":"Cartilage"},{"issue":"6","key":"4155_CR5","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1186\/s13075-014-0485-1","volume":"16","author":"SG Grassel","year":"2014","unstructured":"Grassel SG. The role of peripheral nerve fibers and their neurotransmitters in cartilage and bone physiology and pathophysiology. Arthritis Res Therapy. 2014;16(6):485.","journal-title":"Arthritis Res Therapy"},{"key":"4155_CR6","doi-asserted-by":"crossref","unstructured":"Grassel S, Muschter D. Peripheral nerve fibers and their neurotransmitters in Osteoarthritis Pathology. Int J Mol Sci 2017, 18(5).","DOI":"10.3390\/ijms18050931"},{"key":"4155_CR7","doi-asserted-by":"publisher","first-page":"722884","DOI":"10.3389\/fimmu.2021.722884","volume":"12","author":"S St\u00f6ckl","year":"2021","unstructured":"St\u00f6ckl S, Eitner A, Bauer RJ, K\u00f6nig M, Johnstone B, Gr\u00e4ssel S. Substance P and alpha-calcitonin gene-related peptide differentially affect human osteoarthritic and Healthy Chondrocytes. Front Immunol. 2021;12:722884.","journal-title":"Front Immunol"},{"issue":"1","key":"4155_CR8","doi-asserted-by":"publisher","first-page":"9199","DOI":"10.1038\/s41598-018-27432-y","volume":"8","author":"T Niedermair","year":"2018","unstructured":"Niedermair T, Schirner S, Seebroker R, Straub RH, Grassel S. Substance P modulates bone remodeling properties of murine osteoblasts and osteoclasts. Sci Rep. 2018;8(1):9199.","journal-title":"Sci Rep"},{"key":"4155_CR9","doi-asserted-by":"publisher","first-page":"111265","DOI":"10.1016\/j.mad.2020.111265","volume":"189","author":"T Niedermair","year":"2020","unstructured":"Niedermair T, Schirner S, Lasheras MG, Straub RH, Grassel S. Absence of alpha-calcitonin gene-related peptide modulates bone remodeling properties of murine osteoblasts and osteoclasts in an age-dependent way. Mech Ageing Dev. 2020;189:111265.","journal-title":"Mech Ageing Dev"},{"issue":"5","key":"4155_CR10","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/BF00270017","volume":"98","author":"P Buma","year":"1992","unstructured":"Buma P, Verschuren C, Versleyen D, Van der Oestreicher KP. Calcitonin gene-related peptide, substance P and GAP-43\/B-50 immunoreactivity in the normal and arthrotic knee joint of the mouse. Histochemistry. 1992;98(5):327\u201339.","journal-title":"Histochemistry"},{"issue":"11","key":"4155_CR11","first-page":"1423","volume":"66","author":"S Suri","year":"2007","unstructured":"Suri S, Gill SE, Massena dC, Wilson D, McWilliams DF, Walsh DA. Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis. AnnRheumDis. 2007;66(11):1423\u20138.","journal-title":"AnnRheumDis"},{"issue":"4","key":"4155_CR12","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/0749-8063(90)90054-H","volume":"6","author":"EM Wojtys","year":"1990","unstructured":"Wojtys EM, Beaman DN, Glover RA, Janda D. Innervation of the human knee joint by substance-P fibers. Arthroscopy. 1990;6(4):254\u201363.","journal-title":"Arthroscopy"},{"key":"4155_CR13","doi-asserted-by":"publisher","first-page":"115181","DOI":"10.1016\/j.bone.2019.115181","volume":"133","author":"D Muschter","year":"2020","unstructured":"Muschter D, Fleischhauer L, Taheri S, Schilling AF, Clausen-Schaumann H, Grassel S. Sensory neuropeptides are required for bone and cartilage homeostasis in a murine destabilization-induced osteoarthritis model. Bone. 2020;133:115181.","journal-title":"Bone"},{"issue":"6","key":"4155_CR14","first-page":"695","volume":"15","author":"HL Ma","year":"2007","unstructured":"Ma HL, Blanchet TJ, Peluso D, Hopkins B, Morris EA, Glasson SS. Osteoarthritis severity is sex dependent in a surgical mouse model. OsteoarthritisCartilage. 2007;15(6):695\u2013700.","journal-title":"OsteoarthritisCartilage"},{"key":"4155_CR15","doi-asserted-by":"crossref","unstructured":"Glasson SS, Blanchet TJ, Morris EA. The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129\/SvEv mouse. OsteoarthritisCartilage. 2007;15(9):1061\u20139.","DOI":"10.1016\/j.joca.2007.03.006"},{"key":"4155_CR16","doi-asserted-by":"crossref","unstructured":"Ahmed N, Vogel B, Rohde E, Strunk D, Grifka J, Schulz MB, Grassel S. CD45-positive cells of haematopoietic origin enhance chondrogenic marker gene expression in rat marrow stromal cells. IntJMolMed. 2006;18(2):233\u201340.","DOI":"10.3892\/ijmm.18.2.233"},{"issue":"Suppl 3","key":"4155_CR17","first-page":"S17","volume":"18","author":"SS Glasson","year":"2010","unstructured":"Glasson SS, Chambers MG, van den Berg WB, Little CB. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. OsteoarthritisCartilage. 2010;18(Suppl 3):S17\u201323.","journal-title":"OsteoarthritisCartilage"},{"issue":"1","key":"4155_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1088\/0957-4484\/6\/1\/001","volume":"6","author":"HJ Butt","year":"1995","unstructured":"Butt HJ, Jaschke M. Calculation of thermal noise in Atomic-Force Microscopy. Nanotechnology. 1995;6(1):1\u20137.","journal-title":"Nanotechnology"},{"issue":"6","key":"4155_CR19","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1002\/jmr.855","volume":"20","author":"K Matyka","year":"2007","unstructured":"Matyka K, Matyka M, Mr\u00f3z I, Zalewska-Rejdak J, Ciszewski A. An AFM study on mechanical properties of native and dimethyl suberimidate cross-linked pericardium tissue. J Mol Recognit. 2007;20(6):524\u201330.","journal-title":"J Mol Recognit"},{"issue":"2 Pt 1","key":"4155_CR20","doi-asserted-by":"publisher","first-page":"021914","DOI":"10.1103\/PhysRevE.72.021914","volume":"72","author":"F Rico","year":"2005","unstructured":"Rico F, Roca-Cusachs P, Gavara N, Farr\u00e9 R, Rotger M, Navajas D. Probing mechanical properties of living cells by atomic force microscopy with blunted pyramidal cantilever tips. Phys Rev E Stat Nonlin Soft Matter Phys. 2005;72(2 Pt 1):021914.","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys"},{"key":"4155_CR21","doi-asserted-by":"crossref","unstructured":"Hartmann B, Fleischhauer L, Nicolau M, Jensen THL, Taran FA, Clausen-Schaumann H, Reuten R. Profiling native pulmonary basement membrane stiffness using atomic force microscopy. Nat Protoc 2024.","DOI":"10.1038\/s41596-024-00955-7"},{"key":"4155_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.matbio.2015.10.001","volume":"50","author":"C Prein","year":"2016","unstructured":"Prein C, Warmbold N, Farkas Z, Schieker M, Aszodi A, Clausen-Schaumann H. Structural and mechanical properties of the proliferative zone of the developing murine growth plate cartilage assessed by atomic force microscopy. Matrix Biology: J Int Soc Matrix Biology. 2016;50:1\u201315.","journal-title":"Matrix Biology: J Int Soc Matrix Biology"},{"issue":"11","key":"4155_CR23","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1016\/j.bpj.2010.02.013","volume":"98","author":"M Loparic","year":"2010","unstructured":"Loparic M, Wirz D, Daniels AU, Raiteri R, Vanlandingham MR, Guex G, Martin I, Aebi U, Stolz M. Micro- and nanomechanical analysis of articular cartilage by indentation-type atomic force microscopy: validation with a gel-microfiber composite. Biophys J. 2010;98(11):2731\u201340.","journal-title":"Biophys J"},{"key":"4155_CR24","doi-asserted-by":"publisher","first-page":"801505","DOI":"10.3389\/fimmu.2021.801505","volume":"12","author":"G R\u00f6sch","year":"2021","unstructured":"R\u00f6sch G, Muschter D, Taheri S, El Bagdadi K, Dorn C, Meurer A, Zaucke F, Schilling AF, Gr\u00e4ssel S, Straub RH, et al. \u03b22-Adrenoceptor Deficiency results in increased calcified cartilage thickness and subchondral bone remodeling in murine experimental osteoarthritis. Front Immunol. 2021;12:801505.","journal-title":"Front Immunol"},{"key":"4155_CR25","doi-asserted-by":"crossref","unstructured":"R\u00f6sch G, El Bagdadi K, Muschter D, Taheri S, Dorn C, Meurer A, Straub RH, Zaucke F, Schilling AF, Gr\u00e4ssel S et al. Sympathectomy aggravates subchondral bone changes during osteoarthritis progression in mice without affecting cartilage degeneration or synovial inflammation. Osteoarthritis and cartilage \/ OARS, Osteoarthritis Research Society: 2022, 30(3):461\u2013474.","DOI":"10.1016\/j.joca.2021.11.016"},{"issue":"6","key":"4155_CR26","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1049\/iet-ipr.2014.0490","volume":"9","author":"MJ Fan","year":"2015","unstructured":"Fan MJ, Lee TCM. Variants of seeded region growing. Iet Image Process. 2015;9(6):478\u201385.","journal-title":"Iet Image Process"},{"issue":"3","key":"4155_CR27","doi-asserted-by":"publisher","first-page":"287","DOI":"10.2174\/1573397118666220928141624","volume":"19","author":"S Rosini","year":"2023","unstructured":"Rosini S, Saviola G, Comini L, Molfetta L. Mesenchymal cells are a promising -but still unsatisfying- Anti- inflammatory therapeutic strategy for Osteoarthritis: a narrative review. Curr Rheumatol Rev. 2023;19(3):287\u201393.","journal-title":"Curr Rheumatol Rev"},{"issue":"4","key":"4155_CR28","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nrg3185","volume":"13","author":"C Vogel","year":"2012","unstructured":"Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012;13(4):227\u201332.","journal-title":"Nat Rev Genet"},{"key":"4155_CR29","doi-asserted-by":"publisher","first-page":"24799","DOI":"10.1038\/srep24799","volume":"6","author":"I Kosti","year":"2016","unstructured":"Kosti I, Jain N, Aran D, Butte AJ, Sirota M. Cross-tissue analysis of Gene and protein expression in Normal and Cancer tissues. Sci Rep. 2016;6:24799.","journal-title":"Sci Rep"},{"key":"4155_CR30","doi-asserted-by":"crossref","unstructured":"Alberton P, Dugonitsch HC, Hartmann B, Li P, Farkas Z, Saller MM, Clausen-Schaumann H, Aszodi A. Aggrecan hypomorphism compromises articular cartilage Biomechanical properties and is Associated with increased incidence of spontaneous osteoarthritis. Int J Mol Sci 2019, 20(5).","DOI":"10.3390\/ijms20051008"},{"issue":"3","key":"4155_CR31","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nnano.2008.410","volume":"4","author":"M Stolz","year":"2009","unstructured":"Stolz M, Gottardi R, Raiteri R, Miot S, Martin I, Imer R, Staufer U, Raducanu A, D\u00fcggelin M, Baschong W, et al. Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nat Nanotechnol. 2009;4(3):186\u201392.","journal-title":"Nat Nanotechnol"},{"key":"4155_CR32","doi-asserted-by":"crossref","unstructured":"Benschop RJ, Collins EC, Darling RJ, Allan BW, Leung D, Conner EM, Nelson J, Gaynor B, Xu J, Wang XF et al. Development of a novel antibody to calcitonin gene-related peptide for the treatment of osteoarthritis-related pain. Osteoarthritis and cartilage \/ OARS, Osteoarthritis Research Society: 2014, 22(4):578\u2013585.","DOI":"10.1016\/j.joca.2014.01.009"},{"issue":"1","key":"4155_CR33","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1302\/0301-620X.79B1.0790114","volume":"79","author":"JW Pritchett","year":"1997","unstructured":"Pritchett JW. Substance P level in synovial fluid may predict pain relief after knee replacement. J Bone Joint Surg Br. 1997;79(1):114\u20136.","journal-title":"J Bone Joint Surg Br"},{"key":"4155_CR34","doi-asserted-by":"publisher","first-page":"101658","DOI":"10.1016\/j.bonr.2023.101658","volume":"18","author":"JE Dilley","year":"2023","unstructured":"Dilley JE, Bello MA, Roman N, McKinley T, Sankar U. Post-traumatic osteoarthritis: a review of pathogenic mechanisms and novel targets for mitigation. Bone Rep. 2023;18:101658.","journal-title":"Bone Rep"},{"issue":"1","key":"4155_CR35","first-page":"109","volume":"247","author":"W Schwab","year":"1997","unstructured":"Schwab W, Bilgicyildirim A, Funk RH. Microtopography of the autonomic nerves in the rat knee: a fluorescence microscopic study. AnatRec. 1997;247(1):109\u201318.","journal-title":"AnatRec"},{"key":"4155_CR36","doi-asserted-by":"crossref","unstructured":"Aizah N, Chong PP, Kamarul T, Cartilage. 2021, 13(2_suppl):s1322\u201333.","DOI":"10.1177\/1947603519878479"},{"issue":"1","key":"4155_CR37","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.joca.2022.10.002","volume":"31","author":"S Taheri","year":"2023","unstructured":"Taheri S, Yoshida T, B\u00f6ker KO, Foerster RH, Jochim L, Flux AL, Grosskopf B, Hawellek T, Lehmann W, Schilling AF. Changes of the subchondral bone microchannel network in early osteoarthritis. Osteoarthr Cartil. 2023;31(1):49\u201359.","journal-title":"Osteoarthr Cartil"},{"issue":"9","key":"4155_CR38","doi-asserted-by":"publisher","first-page":"2690","DOI":"10.1002\/art.30307","volume":"63","author":"SM Botter","year":"2011","unstructured":"Botter SM, van Osch GJ, Clockaerts S, Waarsing JH, Weinans H, van Leeuwen JP. Osteoarthritis induction leads to early and temporal subchondral plate porosity in the tibial plateau of mice: an in vivo microfocal computed tomography study. Arthritis Rheum. 2011;63(9):2690\u20139.","journal-title":"Arthritis Rheum"},{"issue":"11","key":"4155_CR39","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/nrrheum.2012.130","volume":"8","author":"DB Burr","year":"2012","unstructured":"Burr DB, Gallant MA. Bone remodelling in osteoarthritis. Nat Rev Rheumatol. 2012;8(11):665\u201373.","journal-title":"Nat Rev Rheumatol"},{"key":"4155_CR40","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3389\/fendo.2020.00077","volume":"11","author":"FX Li","year":"2020","unstructured":"Li FX, Xu F, Lin X, Wu F, Zhong JY, Wang Y, Guo B, Zheng MH, Shan SK, Yuan LQ. The role of Substance P in the regulation of bone and cartilage metabolic activity. Front Endocrinol (Lausanne). 2020;11:77.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"4155_CR41","doi-asserted-by":"crossref","unstructured":"Coaccioli S, Sarzi-Puttini P, Zis P, Rinonapoli G, Varrassi G. Osteoarthritis: New Insight on its pathophysiology. J Clin Med 2022, 11(20).","DOI":"10.3390\/jcm11206013"},{"issue":"4","key":"4155_CR42","doi-asserted-by":"publisher","first-page":"105353","DOI":"10.1016\/j.jbspin.2022.105353","volume":"89","author":"K Liu","year":"2022","unstructured":"Liu K, Chen Y, Miao Y, Xue F, Yin J, Wang L, Li G. Microstructural and histomorphological features of osteophytes in late-stage human knee osteoarthritis with varus deformity. Joint Bone Spine. 2022;89(4):105353.","journal-title":"Joint Bone Spine"},{"key":"4155_CR43","doi-asserted-by":"crossref","unstructured":"Wojcieszek A, Kurowska A, Majda A, Liszka H, G\u0105dek A. The impact of Chronic Pain, Stiffness and difficulties in Performing Daily activities on the quality of life of older patients with knee osteoarthritis. Int J Environ Res Public Health 2022, 19(24).","DOI":"10.3390\/ijerph192416815"},{"issue":"2","key":"4155_CR44","doi-asserted-by":"publisher","first-page":"e22142","DOI":"10.1096\/fj.202101449R","volume":"36","author":"X Fan","year":"2022","unstructured":"Fan X, Wu X, Trevisan Franca De Lima L, Stehbens S, Punyadeera C, Webb R, Hamilton B, Ayyapann V, McLauchlan C, Crawford R, et al. The deterioration of calcified cartilage integrity reflects the severity of osteoarthritis-A structural, molecular, and biochemical analysis. Faseb j. 2022;36(2):e22142.","journal-title":"Faseb j"},{"issue":"1","key":"4155_CR45","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s12891-022-05111-4","volume":"23","author":"Y Wang","year":"2022","unstructured":"Wang Y, Meng F, Wu J, Long H, Li J, Wu Z, He H, Wang H, Wang N, Xie D. Associations between adipokines gene polymorphisms and knee osteoarthritis: a meta-analysis. BMC Musculoskelet Disord. 2022;23(1):166.","journal-title":"BMC Musculoskelet Disord"},{"issue":"6","key":"4155_CR46","doi-asserted-by":"publisher","first-page":"R231","DOI":"10.1186\/ar3218","volume":"12","author":"EH Kang","year":"2010","unstructured":"Kang EH, Lee YJ, Kim TK, Chang CB, Chung JH, Shin K, Lee EY, Lee EB, Song YW. Adiponectin is a potential catabolic mediator in osteoarthritis cartilage. Arthritis Res Therapy. 2010;12(6):R231.","journal-title":"Arthritis Res Therapy"},{"issue":"4","key":"4155_CR47","doi-asserted-by":"publisher","first-page":"R130","DOI":"10.1186\/ar3068","volume":"12","author":"TM Griffin","year":"2010","unstructured":"Griffin TM, Fermor B, Huebner JL, Kraus VB, Rodriguiz RM, Wetsel WC, Cao L, Setton LA, Guilak F. Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice. Arthritis Res Therapy. 2010;12(4):R130.","journal-title":"Arthritis Res Therapy"},{"issue":"10","key":"4155_CR48","doi-asserted-by":"publisher","first-page":"3220","DOI":"10.1002\/art.34533","volume":"64","author":"CR Louer","year":"2012","unstructured":"Louer CR, Furman BD, Huebner JL, Kraus VB, Olson SA, Guilak F. Diet-induced obesity significantly increases the severity of posttraumatic arthritis in mice. Arthritis Rheum. 2012;64(10):3220\u201330.","journal-title":"Arthritis Rheum"},{"issue":"5","key":"4155_CR49","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1210\/en.2016-1510","volume":"158","author":"T Liu","year":"2017","unstructured":"Liu T, Kamiyoshi A, Sakurai T, Ichikawa-Shindo Y, Kawate H, Yang L, Tanaka M, Xian X, Imai A, Zhai L, et al. Endogenous calcitonin gene-related peptide regulates lipid metabolism and energy homeostasis in male mice. Endocrinology. 2017;158(5):1194\u2013206.","journal-title":"Endocrinology"},{"issue":"1","key":"4155_CR50","doi-asserted-by":"publisher","first-page":"17001","DOI":"10.1038\/s41598-021-96545-8","volume":"11","author":"ML H\u00fclser","year":"2021","unstructured":"H\u00fclser ML, Luo Y, Frommer K, Hasseli R, K\u00f6hler K, Diller M, Van Nie L, Rummel C, Roderfeld M, Roeb E, et al. Systemic versus local adipokine expression differs in a combined obesity and osteoarthritis mouse model. Sci Rep. 2021;11(1):17001.","journal-title":"Sci Rep"},{"key":"4155_CR51","doi-asserted-by":"publisher","first-page":"1131198","DOI":"10.3389\/fgene.2023.1131198","volume":"14","author":"D Su","year":"2023","unstructured":"Su D, Ai Y, Zhu G, Yang Y, Ma P. Genetically predicted circulating levels of cytokines and the risk of osteoarthritis: a mendelian randomization study. Front Genet. 2023;14:1131198.","journal-title":"Front Genet"},{"issue":"4","key":"4155_CR52","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1002\/jor.23471","volume":"35","author":"CR Scanzello","year":"2017","unstructured":"Scanzello CR. Chemokines and inflammation in osteoarthritis: insights from patients and animal models. J Orthop Research: Official Publication Orthop Res Soc. 2017;35(4):735\u20139.","journal-title":"J Orthop Research: Official Publication Orthop Res Soc"},{"issue":"12","key":"4155_CR53","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1016\/j.joca.2008.04.027","volume":"16","author":"LJ Sandell","year":"2008","unstructured":"Sandell LJ, Xing X, Franz C, Davies S, Chang LW, Patra D. Exuberant expression of chemokine genes by adult human articular chondrocytes in response to IL-1beta. Osteoarthritis and cartilage \/ OARS. Osteoarthr Res Soc. 2008;16(12):1560\u201371.","journal-title":"Osteoarthr Res Soc"},{"issue":"2","key":"4155_CR54","doi-asserted-by":"publisher","first-page":"C696","DOI":"10.1152\/ajpcell.00060.2007","volume":"293","author":"J Sun","year":"2007","unstructured":"Sun J, Ramnath RD, Bhatia M. Neuropeptide substance P upregulates chemokine and chemokine receptor expression in primary mouse neutrophils. Am J Physiol Cell Physiol. 2007;293(2):C696\u2013704.","journal-title":"Am J Physiol Cell Physiol"}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04155-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-025-04155-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04155-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T14:55:23Z","timestamp":1741186523000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-025-04155-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4155"],"URL":"https:\/\/doi.org\/10.1186\/s13287-025-04155-2","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,5]]},"assertion":[{"value":"26 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Title of the project: Der Einfluss des sensiblen Nervensystems (SP- und alphaCGRP-positive Nervenfasern) auf die OA Pathogenese.The local authorities in W\u00fcrzburg (Regierung von Unterfranken) approved all animal experiments. Approval number: AZ 55.2-2532-2-306. Date of approval: 15th of September 2016.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have not used Artificial Intelligence in this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Usage of AI"}},{"value":"The authors declare that they have no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"117"}}