{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:36:06Z","timestamp":1784223366227,"version":"3.55.0"},"reference-count":57,"publisher":"Frontiers Media SA","content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2018.00269","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T08:52:31Z","timestamp":1522140751000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Halofuginone Attenuates Osteoarthritis by Rescuing Bone Remodeling in Subchondral Bone Through Oral Gavage"],"prefix":"10.3389","volume":"9","author":[{"given":"Wenbo","family":"Mu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hairong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baochao","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdusami","family":"Amat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,3,27]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/sj.neo.7900043","article-title":"Inhibition of neovascularization and tumor growth, and facilitation of wound repair, by halofuginone, an inhibitor of collagen type I synthesis","volume":"1","author":"Abramovitch","year":"1999","journal-title":"Neoplasia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1302\/0301-620X.54B3.409","article-title":"Venous engorgement and intraosseous hypertension in osteoarthritis of the hip","volume":"54","author":"Arnoldi","year":"1972","journal-title":"J. Bone Joint Surg. Br."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1016\/S0140-6736(11)60243-2","article-title":"Osteoarthritis: an update with relevance for clinical practice","volume":"377","author":"Bijlsma","year":"2011","journal-title":"Lancet"},{"key":"B4","first-page":"379","article-title":"Quantification of subchondral bone changes in a murine osteoarthritis model using micro-CT","volume":"43","author":"Botter","year":"2006","journal-title":"Biorheology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1016\/j.joca.2003.09.010","article-title":"The role of joint architecture in the etiology of arthritis","volume":"12","author":"Bullough","year":"2004","journal-title":"Osteoarthr. Cartil."},{"key":"B6","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/nrrheum.2012.130","article-title":"Bone remodelling in osteoarthritis","volume":"8","author":"Burr","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/S0889-857X(03)00061-9","article-title":"Microfractures and microcracks in subchondral bone: are they relevant to osteoarthrosis?","volume":"29","author":"Burr","year":"2003","journal-title":"Rheum. Dis. Clin. North Am."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1038\/nm.2499","article-title":"Targeting osteoclast\u2013osteoblast communication","volume":"17","author":"Cao","year":"2011","journal-title":"Nat. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1016\/S0140-6736(11)60752-6","article-title":"Knee replacement","volume":"379","author":"Carr","year":"2012","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.bcp.2011.09.018","article-title":"Subchondral bone as a key target for osteoarthritis treatment","volume":"83","author":"Casta\u00f1eda","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1136\/annrheumdis-2015-207923","article-title":"Halofuginone attenuates osteoarthritis by inhibition of TGF-\u03b2 activity and H-type vessel formation in subchondral bone","volume":"75","author":"Cui","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"6999","DOI":"10.1182\/blood-2011-01-330142","article-title":"ALK1 as an emerging target for antiangiogenic therapy of cancer","volume":"117","author":"Cunha","year":"2011","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cytogfr.2003.10.004","article-title":"The transforming growth factor-beta superfamily of receptors","volume":"15","author":"de Caestecker","year":"2004","journal-title":"Cytokine Growth Factor Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1016\/j.ejca.2005.12.027","article-title":"Phase, I., and pharmacokinetic study of halofuginone, an oral quinazolinone derivative in patients with advanced solid tumors","volume":"42","author":"De Jonge","year":"2006","journal-title":"Eur. J. Cancer"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.1096\/fj.00-0292com","article-title":"Halofuginone: a potent inhibitor of critical steps in angiogenesis progression","volume":"14","author":"Elkin","year":"2000","journal-title":"FASEB J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"16028","DOI":"10.1038\/boneres.2016.28","article-title":"Bone-cartilage crosstalk: conversation for understanding osteoarthritis","volume":"4","author":"Findlay","year":"2016","journal-title":"Bone Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/pros.10059","article-title":"Growth inhibition of prostate cancer xenografts by halofuginone","volume":"51","author":"Gavish","year":"2002","journal-title":"Prostate"},{"key":"B18","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.joca.2010.05.025","article-title":"The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse","volume":"18","author":"Glasson","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"B19","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1002\/jcp.21258","article-title":"Osteoarthritis","volume":"213","author":"Goldring","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/j.1749-6632.2009.05240.x","article-title":"Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis","volume":"1192","author":"Goldring","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/nrrheum.2016.148","article-title":"Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk","volume":"12","author":"Goldring","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1136\/ard.2011.150607","article-title":"Bone marrow-derived mesenchymal stem cells from early diffuse systemic sclerosis exhibit a paracrine machinery and stimulate angiogenesis in vitro","volume":"70","author":"Guiducci","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"B23","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1699-0463.1999.tb01543.x","article-title":"The long-term effect of a short course of transforming growth factor-beta1 on rat articular cartilage","volume":"107","author":"Itayem","year":"1999","journal-title":"APMIS"},{"key":"B24","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1097\/QAI.0b013e3181fc0141","article-title":"Phase II AIDS Malignancy Consortium trial of topical halofuginone in AIDS-related Kaposi sarcoma","volume":"56","author":"Koon","year":"2011","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1111\/1756-185X.12795","article-title":"Prevalence of knee osteoarthritis, risk factors, and quality of life: the Fifth Korean National Health and Nutrition Examination Survey","volume":"20","author":"Lee","year":"2017","journal-title":"Int. J. Rheum. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: a disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum."},{"key":"B27","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/nrrheum.2010.197","article-title":"The bone-cartilage unit in osteoarthritis","volume":"7","author":"Lories","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.joca.2011.11.015","article-title":"Osteoarthritis year 2011 in review: biology","volume":"20","author":"Lotz","year":"2012","journal-title":"Osteoarthritis Cartilage"},{"key":"B29","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/j.berh.2006.06.009","article-title":"Contemporary concepts of inflammation, damage and repair in rheumatic disease","volume":"20","author":"Luyten","year":"2006","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s00167-010-1054-z","article-title":"The basic science of the subchondral bone","volume":"18","author":"Madry","year":"2010","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"B31","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1016\/j.cub.2011.04.007","article-title":"Conversion of mechanical force into TGF-\u03b2-mediated biochemical signals","volume":"21","author":"Maeda","year":"2011","journal-title":"Curr. Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.joca.2014.01.003","article-title":"OARSI guidelines for the non-surgical management of knee osteoarthritis","volume":"22","author":"McAlindon","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1097\/00007890-199912150-00027","article-title":"Topical treatment of cutaneous chronic graft versus host disease (cGvHD) with halofuginone: a novel inhibitor of collagen type I synthesis","volume":"68","author":"Nagler","year":"1999","journal-title":"Transplantation"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1126\/science.1690453","article-title":"PECAM-1(CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily","volume":"247","author":"Newman","year":"1990","journal-title":"Science"},{"key":"B35","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1002\/dvdy.23992","article-title":"Angiogenesis and intramembranous osteogenesis","volume":"242","author":"Percival","year":"2013","journal-title":"Dev. Dyn."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1016\/j.joca.2011.08.009","article-title":"The effect of osteoarthritis definition on prevalence and incidence estimates: a systematic review","volume":"19","author":"Pereira","year":"2011","journal-title":"Osteoarthr. Cartil."},{"key":"B37","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1517\/17460441.3.1.11","article-title":"Targeting TGF\u03b2 signaling to inhibit fibroblasts activation as a therapy for fibrosis and cancer","volume":"3","author":"Pines","year":"2008","journal-title":"Expert Opin Drug Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"14778","DOI":"10.3748\/wjg.v20.i40.14778","article-title":"Halofuginone for fibrosis, regeneration and cancer in the gastrointestinal tract","volume":"20","author":"Pines","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/S0306-3623(97)00307-8","article-title":"Halofuginone: a novel antifibrotic therapy","volume":"30","author":"Pines","year":"1998","journal-title":"Gen. Pharmacol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"573","DOI":"10.3390\/molecules20010573","article-title":"Halofuginone-the multifaceted molecule","volume":"20","author":"Pines","year":"2015","journal-title":"Molecules"},{"key":"B41","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S1083-8791(03)00151-4","article-title":"Halofuginone to treat fibrosis in chronic graft-versus-host disease and scleroderma","volume":"9","author":"Pines","year":"2003","journal-title":"Biol. Blood Marrow Transplant."},{"key":"B42","doi-asserted-by":"publisher","first-page":"391","DOI":"10.3382\/ps.0740391","article-title":"The effects of halofuginone and salinomycin, alone and in combination, on live performance and skin characteristics of broilers","volume":"74","author":"Pinion","year":"1995","journal-title":"Poult. Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"559","DOI":"10.14670\/HH-27.559","article-title":"Role of angiogenesis on bone formation","volume":"27","author":"Portal-N\u00fa\u00f1ez","year":"2012","journal-title":"Histol. Histopathol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.semarthrit.2014.10.012","article-title":"Socio-economic costs of osteoarthritis: a systematic review of cost-of-illness studies","volume":"44","author":"Puig-Junoy","year":"2015","journal-title":"Semin. Arthritis Rheum."},{"key":"B45","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/nrrheum.2016.136","article-title":"Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis","volume":"12","author":"Robinson","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"14002","DOI":"10.1038\/boneres.2014.2","article-title":"TGF-\u03b2 signaling and the development of osteoarthritis","volume":"2","author":"Shen","year":"2014","journal-title":"Bone Res"},{"key":"B47","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/1471-2474-9-20","article-title":"A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models","volume":"9","author":"Sniekers","year":"2008","journal-title":"BMC Musculoskelet. Disord."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1097\/MPA.0b013e3181da8aa3","article-title":"Inhibition of pancreatic stellate cell activation by halofuginone prevents pancreatic xenograft tumor development","volume":"39","author":"Spector","year":"2010","journal-title":"Pancreas"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1126\/science.1172638","article-title":"Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response","volume":"324","author":"Sundrud","year":"2009","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.bone.2011.10.010","article-title":"Osteochondral alterations in osteoarthritis","volume":"51","author":"Suri","year":"2012","journal-title":"Bone"},{"key":"B51","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1002\/art.39465","article-title":"The prevalence of symptomatic knee osteoarthritis in China: results from China Health and Retirement Longitudinal Study","volume":"68","author":"Tang","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1038\/nm.1979","article-title":"TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation","volume":"15","author":"Tang","year":"2009","journal-title":"Nat. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.joca.2011.01.022","article-title":"Osteoarthritis year 2010 in review: pathomechanisms","volume":"19","author":"van den Berg","year":"2011","journal-title":"Osteoarthritis Cartilage"},{"key":"B54","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1002\/art.1780350715","article-title":"Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy","volume":"35","author":"von der Mark","year":"1992","journal-title":"Arthritis Rheum."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1007\/s40273-016-0424-x","article-title":"Economic and humanistic burden of osteoarthritis: a systematic review of large sample studies","volume":"34","author":"Xie","year":"2016","journal-title":"Pharmacoeconomics"},{"key":"B56","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/nyas.13000","article-title":"Systemic neutralization of TGF-\u03b2 attenuates osteoarthritis","volume":"1376","author":"Xie","year":"2016","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/nm.3143","article-title":"Inhibition of TGF-\u03b2 signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis","volume":"19","author":"Zhen","year":"2013","journal-title":"Nat. Med."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fphar.2018.00269\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T08:52:33Z","timestamp":1522140753000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fphar.2018.00269\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,27]]},"references-count":57,"alternative-id":["10.3389\/fphar.2018.00269"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2018.00269","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,27]]},"article-number":"269"}}