{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:42:07Z","timestamp":1781066527290,"version":"3.54.1"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T00:00:00Z","timestamp":1466985600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T00:00:00Z","timestamp":1466985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We investigated the role of the calcitonin (Miacalcin) in the progression of osteoarthritis (OA) and in nociceptive behavior in an experimental rat model of OA and osteoporosis. OA was induced by anterior cruciate ligament transection (ACLT) of the right knee and by bilateral ovariectomy (OVX) in Wistar rats. Nociceptive behaviors (secondary mechanical allodynia and weight-bearing distribution of the hind paws) were analyzed prior to surgery and every week, beginning at 12 weeks after surgery, up to 20 weeks. At 20 weeks, histopathological studies were performed on the cartilage of the knee joints. Immunohistochemical analysis was performed to examine the effect of calcitonin on transforming growth factor (TGF)-\u03b21 expression in articular cartilage chondrocytes. Rats subjected to ACLT\u2009+\u2009OVX surgery showed obvious OA changes in the joints. Animals subjected to ACLT\u2009+\u2009OVX and treated with calcitonin showed significantly less cartilage degeneration and improved nociceptive tests compared with animals subjected to ACLT\u2009+\u2009OVX surgeries alone. Moreover, calcitonin increased TGF-\u03b21 expression in chondrocytes in ACLT\u2009+\u2009OVX-affected cartilage.<jats:bold>S<\/jats:bold>ubcutaneous injection of calcitonin (1) attenuated the development of OA, (2) concomitantly reduced nociception, and (3) modulated chondrocyte metabolism, possibly by increasing cellular TGF-\u03b21 expression.<\/jats:p>","DOI":"10.1038\/srep28862","type":"journal-article","created":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T09:12:36Z","timestamp":1467018756000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Calcitonin attenuates cartilage degeneration and nociception in an experimental rat model of osteoarthritis: role of TGF-\u03b2 in chondrocytes"],"prefix":"10.1038","volume":"6","author":[{"given":"Zhi-Hong","family":"Wen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Chieh","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Ying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-You","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Peng","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Pai","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Chun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu-Fu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Hsuan","family":"Jean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,27]]},"reference":[{"key":"BFsrep28862_CR1","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1002\/1529-0131(200106)","volume":"44","author":"JP Pelletier","year":"2001","unstructured":"Pelletier, J. P., Martel-Pelletier, J. & Abramson, S. B. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum 44, 1237\u20131247, doi: 10.1002\/1529-0131(200106) (2001).","journal-title":"Arthritis Rheum"},{"key":"BFsrep28862_CR2","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S0304-3959(01)00300-1","volume":"93","author":"P Bajaj","year":"2001","unstructured":"Bajaj, P., Baja, P., Graven-Nielsen, T. & Arendt-Nielsen, L. Osteoarthritis and its association with muscle hyperalgesia: an experimental controlled study. Pain 93, 107\u2013114, doi: 10.1016\/S0304-3959(01)00300-1 (2001).","journal-title":"Pain"},{"key":"BFsrep28862_CR3","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1136\/ard.55.7.424","volume":"55","author":"LS Lohmander","year":"1996","unstructured":"Lohmander, L. S. et al. Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomized, double blind, placebo controlled multicentre trial. Ann Rheum Dis 55, 424\u2013431 (1996).","journal-title":"Ann Rheum Dis"},{"key":"BFsrep28862_CR4","doi-asserted-by":"publisher","first-page":"R169","DOI":"10.1186\/ar1152","volume":"6","author":"P H\u00f8egh-Andersen","year":"2004","unstructured":"H\u00f8egh-Andersen, P. et al. Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application. Arthritis Res Ther 6, R169\u2013180, doi: 10.1186\/ar1152 (2004).","journal-title":"Arthritis Res Ther"},{"key":"BFsrep28862_CR5","doi-asserted-by":"publisher","first-page":"2674","DOI":"10.1002\/art.22797","volume":"56","author":"BC Sondergaard","year":"2007","unstructured":"Sondergaard, B. C., Ostergaard, S., Christiansen, C. & Karsdal, M. A. The effect of oral calcitonin on cartilage turnover and surface erosion in the ovariectomized rat model. Arthritis Rheum 56, 2674\u20132678, doi: 10.1002\/art.22797 (2007).","journal-title":"Arthritis Rheum"},{"key":"BFsrep28862_CR6","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0344-0338(98)80073-3","volume":"194","author":"H Walter","year":"1998","unstructured":"Walter, H. et al. Immunohistochemical analysis of several proteolytic enzymes as parameters of cartilage degradation. Pathol Res Pract 194, 73\u201381, doi: 10.1016\/S0344-0338(98)80073-3 (1998).","journal-title":"Pathol Res Pract"},{"key":"BFsrep28862_CR7","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/S8756-3282(02)00688-9","volume":"30","author":"M Zaidi","year":"2002","unstructured":"Zaidi, M. et al. Forty years of calcitonin\u2014where are we now? A tribute to the work of Iain Macintyre, FRS. Bone 30, 655\u2013663, doi: 10.1016\/S8756-3282(02)00688-9 (2002).","journal-title":"Bone"},{"key":"BFsrep28862_CR8","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1359\/JBMR.040715","volume":"19","author":"LB Tanko","year":"2004","unstructured":"Tanko, L. B. et al. Safety and efficacy of a novel salmon calcitonin (sCT) technology-based oral formulation in healthy postmenopausal women: acute and 3-month effects on biomarkers of bone turnover. J Bone Miner Res 19, 1531\u20138, doi: 10.1359\/JBMR.040715 (2004).","journal-title":"J Bone Miner Res"},{"key":"BFsrep28862_CR9","first-page":"37","volume":"50","author":"J Badurski","year":"1995","unstructured":"Badurski, J., Jeziernicka, E., Naruszewicz, K. & Racewicz, A. Comparative analysis of three treatment regimens for treating gonarthritis with calcitonin, naproxen and flavonoids based on EULAR criteria and visual analogue scale (VAS). Pol Tyg Lek 50, 37\u201340 (1995).","journal-title":"Pol Tyg Lek"},{"key":"BFsrep28862_CR10","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.bone.2005.04.032","volume":"37","author":"YZ Bagger","year":"2005","unstructured":"Bagger, Y. Z. et al. Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis. Bone 37, 425\u2013430, doi: 10.1016\/j.bone.2005.04.032 (2005)","journal-title":"Bone"},{"key":"BFsrep28862_CR11","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.joca.2006.01.014","volume":"14","author":"BC Sondergaard","year":"2006","unstructured":"Sondergaard, B. C. et al. Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes. Osteoarthritis Cartilage 14, 759\u2013768, doi: 10.1016\/j.joca.2006.01.014 (2006).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR12","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/03008200802148355","volume":"49","author":"JP Pujol","year":"2008","unstructured":"Pujol, J. P. et al. Interleukin-1 and transforming growth factor-beta 1 as crucial factors in osteoarthritic cartilage metabolism. Connective Tissue Research 49, 293\u20137, doi: 10.1080\/03008200802148355 (2008).","journal-title":"Connective Tissue Research"},{"key":"BFsrep28862_CR13","first-page":"279","volume":"71","author":"HM van Beuningen","year":"1994","unstructured":"van Beuningen, H. M., van der Kraan, P. M., Arntz, O. J. & van der Berg, W. B. Transforming growth factor-beta 1 stimulates articular chondrocyte proteoglycan synthesis and induces osteophyte formation in the murine knee joint. Lab Invest 71, 279\u2013290 (1994).","journal-title":"Lab Invest"},{"key":"BFsrep28862_CR14","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1083\/jcb.153.1.35","volume":"153","author":"X Yang","year":"2001","unstructured":"Yang, X. et al. TGF-b\/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. J Cell Biol 153, 35\u201346, http:\/\/www.jcb.org\/cgi\/content\/full\/153\/1\/35 (2001).","journal-title":"J Cell Biol"},{"key":"BFsrep28862_CR15","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.joca.2007.02.005","volume":"15","author":"EN Blaney Davidson","year":"2007","unstructured":"Blaney Davidson, E. N., van der Kraan, P. M. & van den Berg, W. B. TGF-beta and osteoarthritis. Osteoarthritis Cartilage 15, 597\u2013604, doi: 10.1016\/j.joca.2007.02.005 (2007).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR16","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.joca.2006.11.008","volume":"1","author":"YH Jean","year":"2007","unstructured":"Jean, Y. H. et al. Intra-articular injection of cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transection knee in rats: role of excitatory amino acids. Osteoarthritis Cartilage 1, 638\u2013645, doi: 10.1016\/j.joca.2006.11.008 (2007).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR17","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","volume":"53","author":"SR Chaplan","year":"1994","unstructured":"Chaplan, S. R. et al. Quantitative assessment of tactile allodynia in the rat paw. 1 J Neuro Meth 53, 55\u201363 (1994).","journal-title":"J Neuro Meth"},{"key":"BFsrep28862_CR18","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.pain.2004.08.004","volume":"112","author":"J Fernihough","year":"2004","unstructured":"Fernihough, J. et al. Pain related behaviour in two models of osteoarthritis in the rat knee. Pain 112, 83\u201393, doi: 10.1016\/j.pain.2004.08.004 (2004).","journal-title":"Pain"},{"key":"BFsrep28862_CR19","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/j.joca.2010.05.012","volume":"18","author":"ZH Wen","year":"2010","unstructured":"Wen, Z. H. et al. Glucosamine sulfate reduces experimental osteoarthritis and nociception in rats: association with changes of mitogen-activated protein kinase in chondrocytes. Osteoarthritis Cartilage 18, 1192\u20131202, doi: 10.1016\/j.joca.2010.05.012 (2010).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR20","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1002\/art.1780380918","volume":"38","author":"JC Fernandes","year":"1995","unstructured":"Fernandes, J. C. et al. Effects of tenidap on canine experimental osteoarthritis. I. Morphologic and metalloprotease analysis. Arthritis Rheum 38, 1290\u20131303, doi: 10.1002\/art.1780380918 (1995).","journal-title":"Arthritis Rheum"},{"key":"BFsrep28862_CR21","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","volume":"214","author":"KP Pritzker","year":"2006","unstructured":"Pritzker, K. P. et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage 214, 13\u201329, doi: 10.1016\/j.joca.2005.07.014 (2006).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR22","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1016\/j.joca.2008.04.008","volume":"16","author":"YH Jean","year":"2008","unstructured":"Jean, Y. H. et al. Increase in excitatory amino acid concentration and transporters expression in osteoarthritic knees of anterior cruciate ligament transected rabbits. Osteoarthritis Cartilage 16, 1442\u20131449, doi: 10.1016\/j.joca.2008.04.008 (2008).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR23","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1016\/j.joca.2009.05.006","volume":"17","author":"CH Lee","year":"2009","unstructured":"Lee, C. H. et al. Intra-articular magnesium sulfate (MgSO4) reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes. Osteoarthritis Cartilage 17, 1485\u201393, doi: 10.1016\/j.joca.2009.05.006 (2009).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR24","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.bbrc.2007.09.030","volume":"363","author":"Y Zhang","year":"2007","unstructured":"Zhang, Y. et al. Doublecortin is expressed in articular chondrocytes. 2 Biochem Biophys Res Commun 363, 694\u2013700, doi: 10.1016\/j.bbrc.2007.09.030 (2007).","journal-title":"Biochem Biophys Res Commun"},{"key":"BFsrep28862_CR25","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/S0140-6736(63)90224-1","volume":"35","author":"MA Kumar","year":"1963","unstructured":"Kumar, M. A., Foster, G. V. & MacIntyre, I. Further evidence for calcitonin. A rapid-acting hormone which lowers plasmacalcium. Lancet 35, 480\u20132 (1963).","journal-title":"Lancet"},{"key":"BFsrep28862_CR26","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1210\/jcem-57-4-819","volume":"57","author":"TJ Chambers","year":"1983","unstructured":"Chambers, T. J. & Moore, A. The sensitivity of isolated osteoclasts to morphological transformation by calcitonin. J Clin Endocrinol Metab 57, 819\u2013824 (1983).","journal-title":"J Clin Endocrinol Metab"},{"key":"BFsrep28862_CR27","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1186\/1756-0500-4-407","volume":"13","author":"T Segovia-Silvestre","year":"2011","unstructured":"Segovia-Silvestre, T. et al. Identification of the calcitonin receptor in osteoarthritic chondrocytes. BMC Res Notes 13, 407 (2011).","journal-title":"BMC Res Notes"},{"key":"BFsrep28862_CR28","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S0026-895X(25)09678-6","volume":"46","author":"RE Kuestner","year":"1994","unstructured":"Kuestner, R. E. et al. Cloning and characterization of an abundant subtype of the human calcitonin receptor. Mol Pharmacol 46, 246\u201355 (1994).","journal-title":"Mol Pharmacol"},{"key":"BFsrep28862_CR29","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.joca.2006.03.014","volume":"14","author":"MA Karsdal","year":"2006","unstructured":"Karsdal, M. A. et al. Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA? Osteoarthritis Cartilage 14, 617\u2013624, doi: 10.1016\/j.joca.2006.03.014 (2006).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR30","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1210\/endo-123-1-159","volume":"123","author":"JR Farley","year":"1988","unstructured":"Farley, J. R. et al. The anti-bone-resorptive agent calcitonin also acts in vitro to directly increase bone formation and bone cell proliferation. Endocrinology 123, 159\u2013167, doi: http:\/\/dx.doi.org\/10.1210\/endo-123-1-159 (1988).","journal-title":"Endocrinology"},{"key":"BFsrep28862_CR31","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S1063-4584(97)80005-2","volume":"5","author":"MP Hellio","year":"1997","unstructured":"Hellio, M. P. et al. Calcitonin inhibits phospholipase A2 and collagenase activity of human osteoarthritic chondrocytes. Osteoarthritis Cartilage 5, 121\u2013128, doi: 10.1016\/S1063-4584(97)80005-2 (1997).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR32","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1002\/art.20124","volume":"50","author":"T Hayami","year":"2004","unstructured":"Hayami, T. et al. The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model. Arthritis Rheum 50, 1193\u20131206, doi: 10.1002\/art.20124 (2004).","journal-title":"Arthritis Rheum"},{"key":"BFsrep28862_CR33","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1002\/1529-0131(199906)","volume":"42","author":"DH Manicourt","year":"1999","unstructured":"Manicourt, D. H. et al. Treatment with calcitonin suppresses the responses of bone, cartilage, and synovium in the early stages of canine experimental osteoarthritis and significantly reduces the severity of the cartilage lesions. Arthritis Rheum 42, 1159\u20131167, doi: 10.1002\/1529-0131(199906) (1999).","journal-title":"Arthritis Rheum"},{"key":"BFsrep28862_CR34","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.joca.2006.09.007","volume":"15","author":"I Meulenbelt","year":"2007","unstructured":"Meulenbelt, I. et al. Clusters of biochemical markers are associated with radiographic subtypes of osteoarthritis (OA) in subject with familial OA at multiple sites. The GARP study. Osteoarthritis Cartilage 15, 379\u2013385, doi: http:\/\/dx.doi.org\/10.1016\/j.joca.2006.09.007 (2007).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR35","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.joca.2006.01.014","volume":"14","author":"BC Sondergaard","year":"2006","unstructured":"Sondergaard, B. C. et al. Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes. Osteoarthritis Cartilage 14, 759\u2013768, doi: http:\/\/dx.doi.org\/10.1016\/j.joca.2006.01.014 (2006).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR36","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.joca.2009.08.004","volume":"18","author":"MA Karsdal","year":"2010","unstructured":"Karsdal, M. A. et al. The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study. Osteoarthritis Cartilage 18, 150\u2013159, doi: 10.1016\/j.joca.2009.08.004 (2010).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR37","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.1152\/jappl.2000.89.6.2359","volume":"89","author":"SK Boyd","year":"2000","unstructured":"Boyd, S. K. et al. Early regional adaptation of periarticular bone mineral density after anterior cruciate ligament injury. J Appl Physiol 89, 2359\u20132364 (2000).","journal-title":"J Appl Physiol"},{"key":"BFsrep28862_CR38","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1152\/jappl.2001.91.1.336","volume":"91","author":"GR Wohl","year":"2001","unstructured":"Wohl, G. R. et al. Periarticular cancellous bone changes following anterior cruciate ligament injury. J Appl Physiol 91, 336\u2013342 (2001).","journal-title":"J Appl Physiol"},{"key":"BFsrep28862_CR39","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1002\/anr.1780320913","volume":"32","author":"BL O\u2019Connor","year":"1989","unstructured":"O\u2019Connor, B. L. et al. Gait alterations in dogs after transection of the anterior cruciate ligament. Arthritis Rheum 32, 1142\u20131147, doi: 10.1002\/anr.1780320913 (1989).","journal-title":"Arthritis Rheum"},{"key":"BFsrep28862_CR40","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1359\/JBMR.040609","volume":"19","author":"C Behets","year":"2004","unstructured":"Behets, C. et al. Effects of calcitonin on subchondral trabecular bone changes and on osteoarthritic cartilage lesions after acute anterior cruciate ligament deficiency. J Bone Miner Res 19, 1821\u20131826, doi: 10.1359\/JBMR.040609 (2004).","journal-title":"J Bone Miner Res"},{"key":"BFsrep28862_CR41","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.joca.2006.06.006","volume":"15","author":"E Calvo","year":"2007","unstructured":"Calvo, E. et al. Osteoporosis increases the severity of cartilage damage in an experimental model of osteoarthritis in rabbits. Osteoarthritis Cartilage 15, 69\u201377, doi: http:\/\/dx.doi.org\/10.1016\/j.joca.2006.06.006 (2007).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR42","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1002\/j.1532-2149.2013.00406.x.","volume":"18","author":"PY Yang","year":"2014","unstructured":"Yang, P. Y. et al. Effects of tibolone on osteoarthritis in ovariectomized rats: association with nociceptive pain behaviour. Eur J Pain 18, 680\u2013690. doi: 10.1002\/j.1532-2149.2013.00406.x. Epub 2013 Oct 2 (2014).","journal-title":"Eur J Pain"},{"key":"BFsrep28862_CR43","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1002\/art.1780381017","volume":"38","author":"DT Felson","year":"1995","unstructured":"Felson, D. T. et al. The incidence and natural history of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum 38, 1500\u20131505, doi: 10.1002\/art.1780381017 (1995).","journal-title":"Arthritis Rheum"},{"key":"BFsrep28862_CR44","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/0014-2999(94)90175-9","volume":"252","author":"MI Colado","year":"1994","unstructured":"Colado, M. I. et al. Involvement of central serotonergic pathways in analgesia elicited by salmon calcitonin in the mouse. Eur J Pharmacol 252, 291\u2013297 (1994).","journal-title":"Eur J Pharmacol"},{"key":"BFsrep28862_CR45","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1159\/000138143","volume":"31","author":"F Guidobono","year":"1985","unstructured":"Guidobono, F. et al. Role of catecholamines in calcitonin-induced analgesia. Pharmacology 31, 342\u2013348 (1985).","journal-title":"Pharmacology"},{"key":"BFsrep28862_CR46","doi-asserted-by":"publisher","first-page":"71S","DOI":"10.1016\/S8756-3282(02)00714-7","volume":"30","author":"GP Lyritis","year":"2002","unstructured":"Lyritis, G. P. & Trovas, G. Analgesic effects of calcitonin. Bone 30, 71S\u20134S (2002).","journal-title":"Bone"},{"key":"BFsrep28862_CR47","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/S0091-3057(98)00015-X","volume":"60","author":"K Shibata","year":"1998","unstructured":"Shibata, K. et al. Ovariectomy-induced hyperalgesia and antinociceptive effect of elcatonin, a synthetic eel calcitonin. Pharmacol Biochem Behav 60, 371\u2013376, doi: 10.1016\/S0091-3057(98)00015-X (1998).","journal-title":"Pharmacol Biochem Behav"},{"key":"BFsrep28862_CR48","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/0304-3959(94)00214-Y","volume":"61","author":"K Elliott","year":"1995","unstructured":"Elliott, K. et al. Dextromethorphan suppresses both formalin-induced nociceptive behavior and the formalin-induced increase in spinal cord c-fos mRNA. Pain 61, 401\u2013409, doi: 10.1016\/0304-3959(94)00214-Y (1995).","journal-title":"Pain"},{"key":"BFsrep28862_CR49","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.neulet.2005.06.044","volume":"11","author":"J Fernihough","year":"2005","unstructured":"Fernihough, J., Gentry, C., Bevan, S. & Winter, J. Regulation of calcitonin gene-related peptide and TRPV1 in a rat model of osteoarthritis. Neurosci Let 11, 388(2), 75\u201380, doi: 10.1016\/j.neulet.2005.06.044 (2005).","journal-title":"Neurosci Let"},{"key":"BFsrep28862_CR50","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1002\/j.1532-2149.2012.00223","volume":"17","author":"AC Ogbonna","year":"2013","unstructured":"Ogbonna, A. C. et al. Pain-like behaviour and spinal changes in the monosodium iodoacetate model of osteoarthritis in C57Bl\/6 mice. Eur J Pain 17, 514\u2013526, doi: 10.1002\/j.1532-2149.2012.00223 (2013).","journal-title":"Eur J Pain"},{"key":"BFsrep28862_CR51","doi-asserted-by":"crossref","unstructured":"Bullock, C. M. et al. Peripheral calcitonin gene-related peptide receptor activation and mechanical sensitization of the joint in rat models of osteoarthritis pain. Arthritis Rheumatol 66, 2188\u20132200, doi: 10.1002\/art.38656.","DOI":"10.1002\/art.38656"},{"key":"BFsrep28862_CR52","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.joca.2006.01.013","volume":"14","author":"RR Castro","year":"2006","unstructured":"Castro, R. R., Cunha, F. Q., Silva, F. S. & Rocha, F.A.C. A quantitative approach to measure joint pain in experimental osteoarthritis-evidence of a role of nitric oxide. Osteoarthritis Cartilage 14, 769\u2013776, doi: 10.1016\/j.joca.2006.01.013 (2006).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR53","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1093\/ajcn\/67.1.18","volume":"67","author":"JW Nieves","year":"1998","unstructured":"Nieves, J. W., Komar, L., Cosman, F. & Lindsay, R. Calcium potentitates the effects of estrogen and calcitonin on bone mass: review and analysis. Am J Clin Nutr 67, 18\u201324 (1998).","journal-title":"Am J Clin Nutr"},{"key":"BFsrep28862_CR54","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1136\/ard.52.3.185","volume":"52","author":"HM van Beuningen","year":"1993","unstructured":"van Beuningen, H. M., van der Kraan, P. M., Arntz, O. J. & van der Berg, W. B. Protection from interleukin 1 induced destruction of articular cartilage by transforming growth factor beta: studies in anatomically intact cartilage in vitro and in vivo . Ann Rheum Dis 52, 185\u2013191 (1993).","journal-title":"Ann Rheum Dis"},{"key":"BFsrep28862_CR55","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1136\/ard.53.9.593","volume":"53","author":"HM van Beuningen","year":"1994","unstructured":"van Beuningen, H. M., van der Kraan, P. M., Arntz, O. J. & van der Berg, W. B. In vivo protection against interleukin-1-induced articular cartilage damage by transforming growth factor-beta 1: age-related differences. Ann Rheum Dis 53, 593\u2013600 (1994).","journal-title":"Ann Rheum Dis"},{"key":"BFsrep28862_CR56","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.2460\/ajvr.2000.61.1003","volume":"61","author":"AA Worster","year":"2000","unstructured":"Worster, A. A., Nixon, A. J., Brower-Toland, B. D. & Williams, J. Effect of transforming growth factor beta1 on chondrogenic differentiation of cultured equine mesenchymal stem cells. Am J Vet Res 61, 1003\u20131010 (2000).","journal-title":"Am J Vet Res"},{"key":"BFsrep28862_CR57","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1016\/j.joca.2009.06.008","volume":"17","author":"PM van der Kraan","year":"2009","unstructured":"van der Kraan, P. M., Blaney Davidson, E. N., Blom, A. & van den Berg, W. B. TGF-beta signaling in chondrocyte terminal differentiation and osteoarthritis: modulation and integration of signaling pathways through receptor-Smads. Osteoarthritis Cartilage 17, 1539\u20131545, doi: 10.1016\/j.joca.2009.06.008 (2009).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR58","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.joca.2014.12.005","volume":"23","author":"EN Blaney Davidson","year":"2015","unstructured":"Blaney Davidson, E. N. et al. TGF-beta is a potent inducer of nerve growth factor in articular cartilage via the ALK5-Smad2\/3 pathway. Potential role in OA related pain? Osteoarthritis Cartilage 23, 478\u2013486, doi: 10.1016\/j.joca.2014.12.005 (2015).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR59","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1136\/ard.2005.045971","volume":"65","author":"EN Blaney Davidson","year":"2006","unstructured":"Blaney Davidson, E. N., Vitters, E. L., van der Kraan, P. M. & van den Berg, W. B. Expression of transforming growth factor-beta (TGFbeta) and the TGFbeta signalling molecule SMAD-2P in spontaneous and instabilityinduced osteoarthritis: role in cartilage degradation, chondrogenesis and osteophyte formation. Ann Rheum Dis 65, 1414\u20131421, doi: 10.1136\/ard.2005.045971 (2006).","journal-title":"Ann Rheum Dis"},{"key":"BFsrep28862_CR60","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.joca.2015.08.013","volume":"24","author":"S Li","year":"2016","unstructured":"Li, S. et al. Vitamin D prevents articular cartilage erosion by regulating collagen II turnover through TGF-\u03b21 in ovariectomized rats. Osteoarthritis Cartilage 24, 345\u2013353, doi: 10.1016\/j.joca.2015.08.013 (2016).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep28862_CR61","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1038\/ng1496","volume":"37","author":"H Kizawa","year":"2005","unstructured":"Kizawa, H. et al. An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet 37, 138\u2013144, doi: 10.1038\/ng1496 (2005).","journal-title":"Nat Genet"},{"key":"BFsrep28862_CR62","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1083\/jcb.139.2.541","volume":"139","author":"R Serra","year":"1997","unstructured":"Serra, R. et al. Expression of a truncated, kinase defective TGF-beta type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis. J Cell Biol 139, 541\u2013552 (1997).","journal-title":"J Cell Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep28862.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep28862","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep28862.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T22:52:51Z","timestamp":1748991171000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep28862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,27]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,6,30]]}},"alternative-id":["BFsrep28862"],"URL":"https:\/\/doi.org\/10.1038\/srep28862","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,27]]},"assertion":[{"value":"21 January 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 June 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28862"}}