{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:35:34Z","timestamp":1783114534636,"version":"3.54.6"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"AOCMF Translational approaches for bone constructs CPP, Sun Yat-sen University Clinical Research 5010 Program","award":["2019009"],"award-info":[{"award-number":["2019009"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102604"],"award-info":[{"award-number":["82102604"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31900583"],"award-info":[{"award-number":["31900583"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32071351"],"award-info":[{"award-number":["32071351"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772400"],"award-info":[{"award-number":["81772400"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016799","name":"Natural Science Foundation of Guangzhou City","doi-asserted-by":"crossref","award":["201807010031"],"award-info":[{"award-number":["201807010031"]}],"id":[{"id":"10.13039\/100016799","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Science and Technology Research Foundation of Guangdong Province","award":["A2022257"],"award-info":[{"award-number":["A2022257"]}]},{"name":"foundation of Shenzhen Committee for foundation of Shenzhen Committee for Science and Technology InnovationScience and Technology Innovation","award":["JCYJ20190809142211354 GJHZ20180929160004704"],"award-info":[{"award-number":["JCYJ20190809142211354 GJHZ20180929160004704"]}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"crossref","award":["SZSM201911002"],"award-info":[{"award-number":["SZSM201911002"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Academic Affairs Office of Sun Yat-sen University","award":["202211583"],"award-info":[{"award-number":["202211583"]}]},{"name":"Academic Affairs Office of Sun Yat-sen University","award":["202211589"],"award-info":[{"award-number":["202211589"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Bone Miner Metab"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>Heterotopic ossification of the tendon and ligament (HOTL) is a chronic progressive disease that is usually accompanied by thickening and ossification of ligaments and high osteogenic activity of the surrounding ligament tissue. However, the molecular mechanism of maintaining the cellular phenotype of HOTL remains unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Materials and methods<\/jats:title>\n                <jats:p>We first constructed a model of HOTL, <jats:italic>Enpp1<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup><jats:italic>\/EIIa-Cre<\/jats:italic> mice, a novel genetic mouse system. Imaging, histological, and cell-level analyses were performed to investigate the progressive ossification of the posterior longitudinal ligament, Achilles tendons, and degeneration joints caused by Enpp1 deficiency.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The results indicate that Enpp1 deficiency led to markedly progressive heterotopic ossification (HO), especially spine, and Achilles tendons, and was associated with progressive degeneration of the knees. The bone mass was decreased in the long bone. Furthermore, fibroblasts from <jats:italic>Enpp1<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup><jats:italic>\/EIIa-Cre<\/jats:italic> mice had greater osteogenic differentiation potential following induction by osteogenesis, accompanied by enhanced hedgehog (Hh) signaling. In addition, fibroblast cells show senescence, and aggravation of the senescence phenotype by further osteogenic induction.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our study indicated that with increasing age, mutations in Enpp1 promote ectopic ossification of spinal ligaments and endochondral ossification in tendons and further aggravate knee degeneration by upregulating hedgehog signaling.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00774-024-01543-1","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T04:02:27Z","timestamp":1724990547000},"page":"681-698","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Enpp1 mutations promote upregulation of hedgehog signaling in heterotopic ossification with aging"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6194-0720","authenticated-orcid":false,"given":"Zhongyuan","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengya","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Tran Canh","family":"Tung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ManMan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xizhe","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"key":"1543_CR1","doi-asserted-by":"publisher","first-page":"5428","DOI":"10.1111\/jcmm.15240","volume":"2410","author":"Q Zhang","year":"2020","unstructured":"Zhang Q, Zhou D, Wang H, Tan J (2020) Heterotopic ossification of tendon and ligament. J Cell Mol Med 2410:5428\u20135437. https:\/\/doi.org\/10.1111\/jcmm.15240","journal-title":"J Cell Mol Med"},{"key":"1543_CR2","first-page":"346","volume":"433","author":"D Shehab","year":"2002","unstructured":"Shehab D, Elgazzar AH, Collier BD (2002) Heterotopic ossification. J Nucl Med 433:346\u2013353","journal-title":"J Nucl Med"},{"key":"1543_CR3","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.bone.2017.09.019","volume":"109","author":"D Cholok","year":"2018","unstructured":"Cholok D, Chung MT, Ranganathan K, Ucer S, Day D, Davis TA, Mishina Y, Levi B (2018) Heterotopic ossification and the elucidation of pathologic differentiation. Bone 109:12\u201321. https:\/\/doi.org\/10.1016\/j.bone.2017.09.019","journal-title":"Bone"},{"key":"1543_CR4","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1007\/s00223-015-0034-1","volume":"975","author":"OG Davies","year":"2015","unstructured":"Davies OG, Grover LM, Eisenstein N, Lewis MP, Liu Y (2015) Identifying the cellular mechanisms leading to heterotopic ossification. Calcif Tissue Int 975:432\u2013444. https:\/\/doi.org\/10.1007\/s00223-015-0034-1","journal-title":"Calcif Tissue Int"},{"key":"1543_CR5","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1038\/mt.2011.101","volume":"198","author":"L Lin","year":"2011","unstructured":"Lin L, Shen Q, Leng H, Duan X, Fu X, Yu C (2011) Synergistic inhibition of endochondral bone formation by silencing Hif1\u03b1 and Runx2 in trauma-induced heterotopic ossification. Mol Therapy J Am Soc Gene Ther 198:1426\u20131432. https:\/\/doi.org\/10.1038\/mt.2011.101","journal-title":"Mol Therapy J Am Soc Gene Ther"},{"key":"1543_CR6","doi-asserted-by":"publisher","first-page":"342","DOI":"10.4062\/biomolther.2019.043","volume":"274","author":"DC Nam","year":"2019","unstructured":"Nam DC, Lee HJ, Lee CJ, Hwang SC (2019) Molecular pathophysiology of ossification of the posterior longitudinal ligament (OPLL). Bio ther 274:342\u2013348. https:\/\/doi.org\/10.4062\/biomolther.2019.043","journal-title":"Bio ther"},{"key":"1543_CR7","doi-asserted-by":"publisher","first-page":"E1460","DOI":"10.1097\/brs.0000000000003648","volume":"4522","author":"H Nakajima","year":"2020","unstructured":"Nakajima H, Watanabe S, Honjoh K, Okawa A, Matsumoto M, Matsumine A (2020) Expression analysis of susceptibility genes for ossification of the posterior longitudinal ligament of the cervical spine in human OPLL-related tissues and a spinal hyperostotic mouse (ttw\/ttw). Spine 4522:E1460-e1468. https:\/\/doi.org\/10.1097\/brs.0000000000003648","journal-title":"Spine"},{"key":"1543_CR8","doi-asserted-by":"publisher","DOI":"10.14336\/ad.2017.0201","author":"L Yan","year":"2017","unstructured":"Yan L, Gao R, Liu Y, He B, Lv S, Hao D (2017) The pathogenesis of ossification of the posterior longitudinal ligament. Aging dis. https:\/\/doi.org\/10.14336\/ad.2017.0201","journal-title":"Aging dis"},{"key":"1543_CR9","doi-asserted-by":"publisher","first-page":"100994","DOI":"10.1016\/j.jbc.2021.100994","volume":"2972","author":"G Jokoji","year":"2021","unstructured":"Jokoji G, Maeda S, Oishi K, Ijuin T, Nakajima M, Tawaratsumida H, Kawamura I, Tominaga H, Taketomi E, Ikegawa S, Taniguchi N (2021) CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1. J biol chem 2972:100994. https:\/\/doi.org\/10.1016\/j.jbc.2021.100994","journal-title":"J biol chem"},{"key":"1543_CR10","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1038\/ng.3045","volume":"469","author":"M Nakajima","year":"2014","unstructured":"Nakajima M, Takahashi A, Tsuji T, Karasugi T, Baba H et al (2014) A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinal ligament of the spine. Nat genet 469:1012\u20131016. https:\/\/doi.org\/10.1038\/ng.3045","journal-title":"Nat genet"},{"key":"1543_CR11","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/956","volume":"193","author":"A Okawa","year":"1998","unstructured":"Okawa A, Nakamura I, Goto S, Moriya H, Nakamura Y, Ikegawa S (1998) Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine. Nat genet 193:271\u2013273. https:\/\/doi.org\/10.1038\/956","journal-title":"Nat genet"},{"key":"1543_CR12","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.tibs.2019.01.010","volume":"447","author":"F Roberts","year":"2019","unstructured":"Roberts F, Zhu D, Farquharson C, Macrae VE (2019) ENPP1 in the regulation of mineralization and beyond. Trends biochem sci 447:616\u2013628. https:\/\/doi.org\/10.1016\/j.tibs.2019.01.010","journal-title":"Trends biochem sci"},{"key":"1543_CR13","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1359\/jbmr.2002.17.1.138","volume":"171","author":"Y Koshizuka","year":"2002","unstructured":"Koshizuka Y, Kawaguchi H, Ogata N, Ikeda T, Mabuchi A, Seichi A, Nakamura Y, Nakamura K, Ikegawa S (2002) Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine. J Bone Min Res Off J Am Soc Bone Min Res 171:138\u2013144. https:\/\/doi.org\/10.1359\/jbmr.2002.17.1.138","journal-title":"J Bone Min Res Off J Am Soc Bone Min Res"},{"key":"1543_CR14","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1007\/s004390050993","volume":"1046","author":"I Nakamura","year":"1999","unstructured":"Nakamura I, Ikegawa S, Okawa A, Okuda S, Koshizuka Y, Kawaguchi H, Nakamura K, Koyama T, Goto S, Toguchida J, Matsushita M, Ochi T, Takaoka K, Nakamura Y (1999) Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL). Hum genet 1046:492\u2013497. https:\/\/doi.org\/10.1007\/s004390050993","journal-title":"Hum genet"},{"key":"1543_CR15","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s003359900707","volume":"92","author":"A Okawa","year":"1998","unstructured":"Okawa A, Ikegawa S, Nakamura I, Goto S, Moriya H, Nakamura Y (1998) Mapping of a gene responsible for twy (tip-toe walking Yoshimura), a mouse model of ossification of the posterior longitudinal ligament of the spine (OPLL). Mammal Genome Off J Internat Mammal Genome Soc 92:155\u2013156. https:\/\/doi.org\/10.1007\/s003359900707","journal-title":"Mammal Genome Off J Internat Mammal Genome Soc"},{"key":"1543_CR16","doi-asserted-by":"publisher","first-page":"115656","DOI":"10.1016\/j.bone.2020.115656","volume":"142","author":"ND Maulding","year":"2021","unstructured":"Maulding ND, Kavanagh D, Zimmerman K, Coppola G, Carpenter TO, Jue NK, Braddock DT (2021) Genetic pathways disrupted by ENPP1 deficiency provide insight into mechanisms of osteoporosis, osteomalacia, and paradoxical mineralization. Bone 142:115656. https:\/\/doi.org\/10.1016\/j.bone.2020.115656","journal-title":"Bone"},{"key":"1543_CR17","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1177\/0022034517744773","volume":"974","author":"V Thumbigere-Math","year":"2018","unstructured":"Thumbigere-Math V, Alqadi A, Chalmers NI, Chavez MB, Chu EY, Collins MT, Ferreira CR, FitzGerald K, Gafni RI, Gahl WA, Hsu KS, Ramnitz MS, Somerman MJ, Ziegler SG, Foster BL (2018) Hypercementosis associated with ENPP1 mutations and GACI. J Dental Res 974:432\u2013441. https:\/\/doi.org\/10.1177\/0022034517744773","journal-title":"J Dental Res"},{"key":"1543_CR18","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1002\/humu.23057","volume":"3711","author":"J Stella","year":"2016","unstructured":"Stella J, Buers I, van de Wetering K, H\u00f6hne W, Rutsch F, Nitschke Y (2016) Effects of different variants in the ENPP1 gene on the functional properties of ectonucleotide pyrophosphatase\/phosphodiesterase family member 1. Hum mutat 3711:1190\u20131201. https:\/\/doi.org\/10.1002\/humu.23057","journal-title":"Hum mutat"},{"key":"1543_CR19","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1002\/jbmr.4550","volume":"37","author":"H Kato","year":"2022","unstructured":"Kato H, Ansh AJ, Lester ER, Kinoshita Y, Hidaka N, Hoshino Y, Koga M, Taniguchi Y, Uchida T, Yamaguchi H, Niida Y, Nakazato M, Nangaku M, Makita N, Takamura T, Saito T, Braddock DT, Ito N (2022) Identification of ENPP1 Haploinsufficiency in patients with diffuse Idiopathic skeletal hyperostosis and early-onset osteoporosis. J Bone Min Res 37:1125\u20131135. https:\/\/doi.org\/10.1002\/jbmr.4550","journal-title":"J Bone Min Res"},{"key":"1543_CR20","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-023-00814-6","author":"H Kato","year":"2023","unstructured":"Kato H, Braddock DT, Ito N (2023) Genetics of diffuse idiopathic skeletal hyperostosis and ossification of the spinal ligaments. Curr Osteoporos Rep. https:\/\/doi.org\/10.1007\/s11914-023-00814-6","journal-title":"Curr Osteoporos Rep"},{"key":"1543_CR21","doi-asserted-by":"publisher","first-page":"7786","DOI":"10.1038\/s41598-017-07341-2","volume":"71","author":"R Watanabe","year":"2017","unstructured":"Watanabe R, Fujita N, Sato Y, Kobayashi T, Morita M, Oike T, Miyamoto K, Kuro OM, Michigami T, Fukumoto S, Tsuji T, Toyama Y, Nakamura M, Matsumoto M, Miyamoto T (2017) Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions. Sci Re 71:7786. https:\/\/doi.org\/10.1038\/s41598-017-07341-2","journal-title":"Sci Re"},{"key":"1543_CR22","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/ng1221","volume":"344","author":"F Rutsch","year":"2003","unstructured":"Rutsch F, Ruf N, Vaingankar S, Toliat MR, Suk A et al (2003) Mutations in ENPP1 are associated with \u201cidiopathic\u201d infantile arterial calcification. Nat genet 344:379\u2013381. https:\/\/doi.org\/10.1038\/ng1221","journal-title":"Nat genet"},{"key":"1543_CR23","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.bone.2012.07.014","volume":"515","author":"NC Mackenzie","year":"2012","unstructured":"Mackenzie NC, Huesa C, Rutsch F, MacRae VE (2012) New insights into NPP1 function: lessons from clinical and animal studies. Bone 515:961\u2013968. https:\/\/doi.org\/10.1016\/j.bone.2012.07.014","journal-title":"Bone"},{"key":"1543_CR24","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7455","author":"J Zhang","year":"2016","unstructured":"Zhang J, Dyment NA, Rowe DW, Siu SY, Sundberg JP, Uitto J, Li Q (2016) Ectopic mineralization of cartilage and collagen-rich tendons and ligaments in Enpp1asj-2J mice. Oncotarget. https:\/\/doi.org\/10.18632\/oncotarget.7455","journal-title":"Oncotarget"},{"key":"1543_CR25","doi-asserted-by":"publisher","DOI":"10.1242\/dev.164830","author":"Y Jin","year":"2018","unstructured":"Jin Y, Cong Q, Gvozdenovic-Jeremic J, Hu J, Zhang Y, Terkeltaub R, Yang Y (2018) Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling. Development (Cambridge, England). https:\/\/doi.org\/10.1242\/dev.164830","journal-title":"Development (Cambridge, England)"},{"key":"1543_CR26","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1002\/jor.23743","volume":"364","author":"S Hiratsuka","year":"2018","unstructured":"Hiratsuka S, Takahata M, Shimizu T, Hamano H, Ota M, Sato D, Iwasaki N (2018) Drug therapy targeting pyrophosphate slows the ossification of spinal ligaments in twy mice. J Orthop Res Off Pub Orthop Res Soc 364:1256\u20131261. https:\/\/doi.org\/10.1002\/jor.23743","journal-title":"J Orthop Res Off Pub Orthop Res Soc"},{"key":"1543_CR27","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/nrm3598","volume":"147","author":"J Briscoe","year":"2013","unstructured":"Briscoe J, Th\u00e9rond PP (2013) The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol 147:416\u2013429. https:\/\/doi.org\/10.1038\/nrm3598","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1543_CR28","doi-asserted-by":"publisher","first-page":"17905","DOI":"10.1074\/jbc.R112.356006","volume":"28722","author":"KE Ryan","year":"2012","unstructured":"Ryan KE, Chiang C (2012) Hedgehog secretion and signal transduction in vertebrates. J Biol Chem 28722:17905\u201317913. https:\/\/doi.org\/10.1074\/jbc.R112.356006","journal-title":"J Biol Chem"},{"key":"1543_CR29","doi-asserted-by":"publisher","first-page":"3743","DOI":"10.1007\/s00018-021-03806-w","volume":"787","author":"BA Allard","year":"2021","unstructured":"Allard BA, Wang W, Pottorf TS, Mumtaz H, Jack BM, Wang HH, Silva LM, Jacobs DT, Wang J, Bumann EE, Tran PV (2021) Thm2 interacts with paralog, Thm1, and sensitizes to Hedgehog signaling in postnatal skeletogenesis. Cell Mol Life Sci CMLS 787:3743\u20133762. https:\/\/doi.org\/10.1007\/s00018-021-03806-w","journal-title":"Cell Mol Life Sci CMLS"},{"key":"1543_CR30","doi-asserted-by":"publisher","first-page":"956","DOI":"10.7150\/ijbs.65954","volume":"183","author":"J Wu","year":"2022","unstructured":"Wu J, Wang R, Kan X, Zhang J, Sun W, Goltzman D, Miao D (2022) A Sonic Hedgehog-Gli-Bmi1 signaling pathway plays a critical role in p27 deficiency induced bone anabolism. Internat J Biol Sci 183:956\u2013969. https:\/\/doi.org\/10.7150\/ijbs.65954","journal-title":"Internat J Biol Sci"},{"key":"1543_CR31","doi-asserted-by":"publisher","DOI":"10.1242\/dev.199826","author":"DJ Hoyle","year":"2022","unstructured":"Hoyle DJ, Dranow DB, Schilling TF (2022) Pthlha and mechanical force control early patterning of growth zones in the zebrafish craniofacial skeleton. Development (Cambridge, England). https:\/\/doi.org\/10.1242\/dev.199826","journal-title":"Development (Cambridge, England)"},{"key":"1543_CR32","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1359\/jbmr.041210","volume":"204","author":"A Sakamoto","year":"2005","unstructured":"Sakamoto A, Chen M, Kobayashi T, Kronenberg HM, Weinstein LS (2005) Chondrocyte-specific knockout of the G protein G(s)alpha leads to epiphyseal and growth plate abnormalities and ectopic chondrocyte formation. J Bone Min Res Off J Am Soc Bone Min Res 204:663\u2013671. https:\/\/doi.org\/10.1359\/jbmr.041210","journal-title":"J Bone Min Res Off J Am Soc Bone Min Res"},{"key":"1543_CR33","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1007\/s00774-021-01271-w","volume":"401","author":"Q Liang","year":"2022","unstructured":"Liang Q, Lu Y, Yu L, Zhu Q, Xie W, Wang Y, Ye L, Li Q, Liu S, Liu Y, Zhu C (2022) Disruption of the mouse Bmal1 locus promotes heterotopic ossification with aging via TGF-beta\/BMP signaling. J bone Min Metabol 401:40\u201355. https:\/\/doi.org\/10.1007\/s00774-021-01271-w","journal-title":"J bone Min Metabol"},{"key":"1543_CR34","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.biocel.2018.11.008","volume":"106","author":"MF Ahmed","year":"2019","unstructured":"Ahmed MF, El-Sayed AK, Chen H, Zhao R, Jin K, Zuo Q, Zhang Y, Li B (2019) Direct conversion of mouse embryonic fibroblast to osteoblast cells using hLMP-3 with Yamanaka factors. Internat J Biochem Cell Biol 106:84\u201395. https:\/\/doi.org\/10.1016\/j.biocel.2018.11.008","journal-title":"Internat J Biochem Cell Biol"},{"key":"1543_CR35","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1002\/jbmr.3911","volume":"353","author":"R Oheim","year":"2020","unstructured":"Oheim R, Zimmerman K, Maulding ND, St\u00fcrznickel J, von Kroge S, Kavanagh D, Stabach PR, Kornak U, Tommasini SM, Horowitz MC, Amling M, Thompson D, Schinke T, Busse B, Carpenter TO, Braddock DT (2020) Human Heterozygous ENPP1 deficiency is associated with early onset osteoporosis, a phenotype recapitulated in a mouse model of enpp1 deficiency. J Bone Min Rese Off J Am Soc Bone Min Res 353:528\u2013539. https:\/\/doi.org\/10.1002\/jbmr.3911","journal-title":"J Bone Min Rese Off J Am Soc Bone Min Res"},{"key":"1543_CR36","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1007\/s00125-015-3837-8","volume":"593","author":"I Sandovici","year":"2016","unstructured":"Sandovici I, Hammerle CM, Cooper WN, Smith NH, Tarry-Adkins JL, Dunmore BJ, Bauer J, Andrews SR, Yeo GS, Ozanne SE, Const\u00e2ncia M (2016) Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets. Diabetologia 593:502\u2013511. https:\/\/doi.org\/10.1007\/s00125-015-3837-8","journal-title":"Diabetologia"},{"key":"1543_CR37","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1111\/exd.14498","volume":"314","author":"E Koz\u00e1k","year":"2022","unstructured":"Koz\u00e1k E, F\u00fcl\u00f6p K, T\u0151k\u00e9si N, Rao N, Li Q, Terry SF, Uitto J, Zhang X, Becker C, V\u00e1radi A, Pomozi V (2022) Oral supplementation of inorganic pyrophosphate in pseudoxanthoma elasticum. Exp Dermatol 314:548\u2013555. https:\/\/doi.org\/10.1111\/exd.14498","journal-title":"Exp Dermatol"},{"key":"1543_CR38","doi-asserted-by":"publisher","first-page":"8876","DOI":"10.1096\/fj.201903216RR","volume":"347","author":"Y Yang","year":"2020","unstructured":"Yang Y, Lin Z, Cheng J, Ding S, Mao WW, Shi S, Liang B, Jiang L (2020) The roles of autophagy in osteogenic differentiation in rat ligamentum fibroblasts: Evidence and possible implications. FASEB J Off Pub Fed Am Soc Exp Biol 347:8876\u20138886. https:\/\/doi.org\/10.1096\/fj.201903216RR","journal-title":"FASEB J Off Pub Fed Am Soc Exp Biol"},{"key":"1543_CR39","doi-asserted-by":"publisher","first-page":"115517","DOI":"10.1016\/j.bone.2020.115517","volume":"139","author":"AL Strong","year":"2020","unstructured":"Strong AL, Spreadborough PJ, Pagani CA, Haskins RM, Dey D, Grimm PD, Kaneko K, Marini S, Huber AK, Hwang C, Westover K, Mishina Y, Bradley MJ, Levi B, Davis TA (2020) Small molecule inhibition of non-canonical (TAK1-mediated) BMP signaling results in reduced chondrogenic ossification and heterotopic ossification in a rat model of blast-associated combat-related lower limb trauma. Bone 139:115517. https:\/\/doi.org\/10.1016\/j.bone.2020.115517","journal-title":"Bone"},{"key":"1543_CR40","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.gpb.2018.04.006","volume":"163","author":"EL Crowgey","year":"2018","unstructured":"Crowgey EL, Wyffels JT, Osborn PM, Wood TT, Edsberg LE (2018) A systems biology approach for studying heterotopic ossification: proteomic analysis of clinical serum and tissue samples. Genom Proteom Bioinformat 163:212\u2013220. https:\/\/doi.org\/10.1016\/j.gpb.2018.04.006","journal-title":"Genom Proteom Bioinformat"},{"key":"1543_CR41","doi-asserted-by":"publisher","first-page":"E1388","DOI":"10.1097\/BRS.0b013e3182a40489","volume":"3822","author":"D Sugita","year":"2013","unstructured":"Sugita D, Yayama T, Uchida K, Kokubo Y, Nakajima H, Yamagishi A, Takeura N, Baba H (2013) Indian hedgehog signaling promotes chondrocyte differentiation in enchondral ossification in human cervical ossification of the posterior longitudinal ligament. Spine 3822:E1388-1396. https:\/\/doi.org\/10.1097\/BRS.0b013e3182a40489","journal-title":"Spine"},{"key":"1543_CR42","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.bone.2014.09.016","volume":"69","author":"MO Hajjawi","year":"2014","unstructured":"Hajjawi MO, MacRae VE, Huesa C, Boyde A, Mill\u00e1n JL, Arnett TR, Orriss IR (2014) Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-\/-) mice. Bone 69:139\u2013147. https:\/\/doi.org\/10.1016\/j.bone.2014.09.016","journal-title":"Bone"},{"key":"1543_CR43","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1471-2474-11-19","volume":"11","author":"Y Sun","year":"2010","unstructured":"Sun Y, Mauerhan DR, Honeycutt PR, Kneisl JS, Norton JH, Hanley EN Jr, Gruber HE (2010) Analysis of meniscal degeneration and meniscal gene expression. BMC Musculoskelet Disord 11:19. https:\/\/doi.org\/10.1186\/1471-2474-11-19","journal-title":"BMC Musculoskelet Disord"},{"key":"1543_CR44","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1089\/scd.2020.0117","volume":"2924","author":"Z Cai","year":"2020","unstructured":"Cai Z, Wu B, Ye G, Liu W, Chen K, Wang P, Xie Z, Li J, Zheng G, Yu W, Su Z, Lin J, Wu Y, Shen H (2020) Enhanced osteogenic differentiation of human bone marrow mesenchymal stem cells in ossification of the posterior longitudinal ligament through activation of the BMP2-Smad1\/5\/8 pathway. Stem cells dev 2924:1567\u20131576. https:\/\/doi.org\/10.1089\/scd.2020.0117","journal-title":"Stem cells dev"},{"key":"1543_CR45","doi-asserted-by":"publisher","first-page":"7231","DOI":"10.1038\/s41598-020-64304-w","volume":"101","author":"D Sugita","year":"2020","unstructured":"Sugita D, Nakajima H, Kokubo Y, Takeura N, Yayama T, Matsumine A (2020) Cyclic tensile strain facilitates ossification of the cervical posterior longitudinal ligament via increased Indian hedgehog signaling. Sci Rep 101:7231. https:\/\/doi.org\/10.1038\/s41598-020-64304-w","journal-title":"Sci Rep"},{"key":"1543_CR46","doi-asserted-by":"publisher","first-page":"6354","DOI":"10.1172\/jci132518","volume":"13012","author":"H Feng","year":"2020","unstructured":"Feng H, Xing W, Han Y, Sun J, Kong M, Gao B, Yang Y, Yin Z, Chen X, Zhao Y, Bi Q, Zou W (2020) Tendon-derived cathepsin K-expressing progenitor cells activate Hedgehog signaling to drive heterotopic ossification. J Clin Investig 13012:6354\u20136365. https:\/\/doi.org\/10.1172\/jci132518","journal-title":"J Clin Investig"}],"container-title":["Journal of Bone and Mineral Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00774-024-01543-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00774-024-01543-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00774-024-01543-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T07:38:09Z","timestamp":1733902689000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00774-024-01543-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,30]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["1543"],"URL":"https:\/\/doi.org\/10.1007\/s00774-024-01543-1","relation":{},"ISSN":["0914-8779","1435-5604"],"issn-type":[{"value":"0914-8779","type":"print"},{"value":"1435-5604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,30]]},"assertion":[{"value":"8 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declared no potential conflicts of interest to this article's research, authorship and publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The studies were reviewed and approved by the Institutional Animal Care and Use Committee, Sun Yat-Sen University (No. 2020000147).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}