{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:07:58Z","timestamp":1792123678721,"version":"4.4.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T00:00:00Z","timestamp":1515715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T00:00:00Z","timestamp":1521849600000},"content-version":"vor","delay-in-days":71,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81371990 to DC"],"award-info":[{"award-number":["81371990 to DC"]}],"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":["81530070"],"award-info":[{"award-number":["81530070"]}],"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":["81625015"],"award-info":[{"award-number":["81625015"]}],"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":["U1301222"],"award-info":[{"award-number":["U1301222"]}],"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":["31529002 to XB"],"award-info":[{"award-number":["31529002 to XB"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Vascular-invasion-mediated interactions between activated articular chondrocytes and subchondral bone are essential for osteoarthritis (OA) development. Here, we determined the role of nutrient sensing mechanistic target of rapamycin complex 1 (mTORC1) signaling in the crosstalk across the bone cartilage interface and its regulatory mechanisms. Then mice with chondrocyte-specific mTORC1 activation (Tsc1 CKO and Tsc1 CKOER) or inhibition (Raptor CKOER) and their littermate controls were subjected to OA induced by destabilization of the medial meniscus (DMM) or not. DMM or Tsc1 CKO mice were treated with bevacizumab, a vascular endothelial growth factor (VEGF)-A antibody that blocks angiogenesis. Articular cartilage degeneration was evaluated using the Osteoarthritis Research Society International score. Immunostaining and Western blotting were conducted to detect H-type vessels and protein levels in mice. Primary chondrocytes from mutant mice and ADTC5 cells were treated with interleukin-1\u03b2 to investigate the role of chondrocyte mTORC1 in VEGF-A secretion and in vitro vascular formation. Clearly, H-type vessels were increased in subchondral bone in DMM-induced OA and aged mice. Cartilage mTORC1 activation stimulated VEGF-A production in articular chondrocyte and H-type vessel formation in subchondral bone. Chondrocyte mTORC1 promoted OA partially through formation of VEGF-A\u2013stimulated subchondral H-type vessels. In particular, vascular-derived nutrients activated chondrocyte mTORC1, and stimulated chondrocyte activation and production of VEGF, resulting in further angiogenesis in subchondral bone. Thus a positive-feedback regulation of H-type vessel formation in subchondral bone by articular chondrocyte nutrient-sensing mTORC1 signaling is essential for the pathogenesis and progression of OA. \u00a9 2018 American Society for Bone and Mineral Research<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.3388","type":"journal-article","created":{"date-parts":[[2018,1,13]],"date-time":"2018-01-13T07:29:53Z","timestamp":1515828593000},"page":"909-920","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Positive-Feedback Regulation of Subchondral H-Type Vessel Formation by Chondrocyte Promotes Osteoarthritis Development in Mice"],"prefix":"10.1093","volume":"33","author":[{"given":"Jiansen","family":"Lu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organ Failure ResearchDepartment of Cell BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina"},{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daozhang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinglin","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Shao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure ResearchDepartment of Cell BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina"},{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure ResearchDepartment of Cell BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina"},{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayao","family":"Ouyang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure ResearchDepartment of Cell BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina"},{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denghui","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical EngineeringMaterials Research InstitutesThe Huck Institutes of The Life SciencesThe Pennsylvania State UniversityUniversity ParkPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical BiologyUniversity of Pittsburgh School of MedicinePittsburghPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Bai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure ResearchDepartment of Cell BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina"},{"name":"Department of OrthopedicsAcademy of Orthopedics, Guangdong ProvinceOrthopedic Hospital of Guangdong ProvinceThe Third Affiliated Hospital of Southern Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,1,12]]},"reference":[{"issue":"9991","key":"2024021014340375900_jbmr3388-bib-0001","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0140-6736(14)60802-3","article-title":"Osteoarthritis","volume":"386","author":"Glyn-Jones","year":"2015","journal-title":"Lancet"},{"issue":"11","key":"2024021014340375900_jbmr3388-bib-0002","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nrrheum.2016.162","article-title":"The danger from within: alarmins in arthritis","volume":"12","author":"Nefla","year":"2016","journal-title":"Nat Rev Rheumatol"},{"issue":"9783","key":"2024021014340375900_jbmr3388-bib-0003","doi-asserted-by":"crossref","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"},{"issue":"5","key":"2024021014340375900_jbmr3388-bib-0004","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nrrheum.2017.50","article-title":"The role of metabolism in the pathogenesis of osteoarthritis","volume":"13","author":"Mobasheri","year":"2017","journal-title":"Nat Rev Rheumatol"},{"issue":"16","key":"2024021014340375900_jbmr3388-bib-0005","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1056\/NEJMoa0901510","article-title":"Tanezumab for the treatment of pain from osteoarthritis of the knee","volume":"363","author":"Lane","year":"2010","journal-title":"N Engl J Med"},{"issue":"3","key":"2024021014340375900_jbmr3388-bib-0006","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1136\/annrheumdis-2013-203913","article-title":"Quality indicators for the primary care of osteoarthritis: a systematic review","volume":"74","author":"Edwards","year":"2015","journal-title":"Ann Rheum Dis"},{"issue":"11","key":"2024021014340375900_jbmr3388-bib-0007","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nrrheum.2011.129","article-title":"Cartilage biology in osteoarthritis\u2014lessons from developmental biology","volume":"7","author":"Pitsillides","year":"2011","journal-title":"Nat Rev Rheumatol"},{"issue":"3","key":"2024021014340375900_jbmr3388-bib-0008","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.joca.2011.12.003","article-title":"Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration","volume":"20","author":"van der Kraan","year":"2012","journal-title":"Osteoarthritis Cartilage"},{"key":"2024021014340375900_jbmr3388-bib-0009","doi-asserted-by":"crossref","first-page":"10959","DOI":"10.1038\/ncomms10959","article-title":"Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3","volume":"7","author":"Yahara","year":"2016","journal-title":"Nat Commun"},{"issue":"10","key":"2024021014340375900_jbmr3388-bib-0010","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nrrheum.2015.95","article-title":"Cartilage damage in osteoarthritis and rheumatoid arthritis\u2014two unequal siblings","volume":"11","author":"Pap","year":"2015","journal-title":"Nat Rev Rheumatol"},{"issue":"Suppl 2","key":"2024021014340375900_jbmr3388-bib-0011","doi-asserted-by":"crossref","first-page":"ii78","DOI":"10.1136\/ard.61.suppl_2.ii78","article-title":"Type II collagen degradation and its regulation in articular cartilage in osteoarthritis","volume":"61","author":"Poole","year":"2002","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"2024021014340375900_jbmr3388-bib-0012","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nm.3143","article-title":"Inhibition of TGF-beta signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis","volume":"19","author":"Zhen","year":"2013","journal-title":"Nat Med"},{"issue":"4","key":"2024021014340375900_jbmr3388-bib-0013","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/BOR.0000000000000181","article-title":"Subchondral bone and osteoarthritis","volume":"27","author":"Funck-Brentano","year":"2015","journal-title":"Curr Opin Rheumatol"},{"issue":"5","key":"2024021014340375900_jbmr3388-bib-0014","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/ard.2007.073023","article-title":"Correlation between bone lesion changes and cartilage volume loss in patients with osteoarthritis of the knee as assessed by quantitative magnetic resonance imaging over a 24-month period","volume":"67","author":"Raynauld","year":"2008","journal-title":"Ann Rheum Dis"},{"issue":"10","key":"2024021014340375900_jbmr3388-bib-0015","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1002\/art.30471","article-title":"Quantitative magnetic resonance imaging evidence of synovial proliferation is associated with radiographic severity of knee osteoarthritis","volume":"63","author":"Krasnokutsky","year":"2011","journal-title":"Arthritis Rheum"},{"issue":"11","key":"2024021014340375900_jbmr3388-bib-0016","doi-asserted-by":"crossref","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"},{"issue":"2","key":"2024021014340375900_jbmr3388-bib-0017","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1136\/annrheumdis-2013-204111","article-title":"The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments","volume":"73","author":"Karsdal","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"2024021014340375900_jbmr3388-bib-0018","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jbiomech.2016.12.025","article-title":"Solute transport at the interface of cartilage and subchondral bone plate: effect of micro-architecture","volume":"52","author":"Pouran","year":"2017","journal-title":"J Biomech"},{"issue":"3","key":"2024021014340375900_jbmr3388-bib-0019","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3899\/jrheum.110777","article-title":"Aggravation of ADAMTS and matrix metalloproteinase production and role of ERK1\/2 pathway in the interaction of osteoarthritic subchondral bone osteoblasts and articular cartilage chondrocytes\u2014possible pathogenic role in osteoarthritis","volume":"39","author":"Prasadam","year":"2012","journal-title":"J Rheumatol"},{"issue":"11","key":"2024021014340375900_jbmr3388-bib-0020","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1136\/ard.2005.039263","article-title":"Is progressive osteoarthritis an atheromatous vascular disease","volume":"64","author":"Conaghan","year":"2005","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"2024021014340375900_jbmr3388-bib-0021","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1749-6632.2009.05376.x","article-title":"Noninvasive methods of measuring bone blood perfusion","volume":"1192","author":"Dyke","year":"2010","journal-title":"Ann N Y Acad Sci"},{"issue":"7","key":"2024021014340375900_jbmr3388-bib-0022","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s002560050254","article-title":"Degenerative joint disease: cartilage or vascular disease","volume":"26","author":"Imhof","year":"1997","journal-title":"Skelet Radiol"},{"issue":"3","key":"2024021014340375900_jbmr3388-bib-0023","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1097\/00002142-199906000-00002","article-title":"Importance of subchondral bone to articular cartilage in health and disease","volume":"10","author":"Imhof","year":"1999","journal-title":"Top Magn Reson Imaging"},{"issue":"1","key":"2024021014340375900_jbmr3388-bib-0024","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1196\/annals.1402.069","article-title":"Perfusion abnormalities in subchondral bone associated with marrow edema, osteoarthritis, and avascular necrosis","volume":"1117","author":"Aaron","year":"2007","journal-title":"Ann N Y Acad Sci"},{"issue":"12","key":"2024021014340375900_jbmr3388-bib-0025","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1016\/j.joca.2013.08.018","article-title":"Consequences of chondrocyte hypertrophy on osteoarthritic cartilage: potential effect on angiogenesis","volume":"21","author":"Pesesse","year":"2013","journal-title":"Osteoarthritis Cartilage"},{"issue":"Suppl C","key":"2024021014340375900_jbmr3388-bib-0026","doi-asserted-by":"crossref","first-page":"C109","DOI":"10.1016\/S1063-4584(07)61818-4","article-title":"Study of in vitro conditions promoting hypertrophic differentiation of osteoarthritic articular chondrocytes [Abstract]","volume":"15","author":"Sanchez","year":"2007","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"2024021014340375900_jbmr3388-bib-0027","doi-asserted-by":"crossref","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"},{"issue":"2","key":"2024021014340375900_jbmr3388-bib-0028","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.bone.2011.11.030","article-title":"Elevated cross-talk between subchondral bone and cartilage in osteoarthritic joints","volume":"51","author":"Pan","year":"2012","journal-title":"Bone"},{"issue":"1","key":"2024021014340375900_jbmr3388-bib-0029","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrm3025","article-title":"mTOR: from growth signal integration to cancer, diabetes and ageing","volume":"12","author":"Zoncu","year":"2011","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"2024021014340375900_jbmr3388-bib-0030","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nrrheum.2015.172","article-title":"Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases","volume":"12","author":"Perl","year":"2016","journal-title":"Nat Rev Rheumatol"},{"issue":"1","key":"2024021014340375900_jbmr3388-bib-0031","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s40268-015-0082-z","article-title":"mTOR: a potential therapeutic target in osteoarthritis","volume":"15","author":"Pal","year":"2015","journal-title":"Drugs R D"},{"issue":"37","key":"2024021014340375900_jbmr3388-bib-0032","doi-asserted-by":"crossref","first-page":"9904","DOI":"10.1016\/j.biomaterials.2014.08.041","article-title":"Intra-articular administration of gelatin hydrogels incorporating rapamycin-micelles reduces the development of experimental osteoarthritis in a murine model","volume":"35","author":"Matsuzaki","year":"2014","journal-title":"Biomaterials"},{"issue":"7","key":"2024021014340375900_jbmr3388-bib-0033","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1136\/annrheumdis-2013-204599","article-title":"Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis","volume":"74","author":"Zhang","year":"2015","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"2024021014340375900_jbmr3388-bib-0034","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/annrheumdis-2011-200557","article-title":"Autophagy activation by rapamycin reduces severity of experimental osteoarthritis","volume":"71","author":"Carames","year":"2012","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"2024021014340375900_jbmr3388-bib-0035","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.joca.2016.12.024","article-title":"mTORC1 activation downregulates FGFR3 and PTH\/PTHrP receptor in articular chondrocytes to initiate osteoarthritis","volume":"25","author":"Zhang","year":"2017","journal-title":"Osteoarthritis Cartilage"},{"key":"2024021014340375900_jbmr3388-bib-0036","doi-asserted-by":"crossref","first-page":"11151","DOI":"10.1038\/ncomms11151","article-title":"mTORC1 regulates PTHrP to coordinate chondrocyte growth, proliferation and differentiation","volume":"7","author":"Yan","year":"2016","journal-title":"Nat Commun"},{"issue":"1","key":"2024021014340375900_jbmr3388-bib-0037","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/art.39425","article-title":"Inhibition of osteoarthritis by adipose-derived stromal cells overexpressing Fra-1 in mice","volume":"68","author":"Schwabe","year":"2016","journal-title":"Arthritis Rheumatol"},{"issue":"5","key":"2024021014340375900_jbmr3388-bib-0038","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.tips.2014.03.005","article-title":"Targeting TGF\u03b2 signaling in subchondral bone and articular cartilage homeostasis","volume":"35","author":"Zhen","year":"2014","journal-title":"Trends Pharmacol Sci"},{"issue":"7","key":"2024021014340375900_jbmr3388-bib-0039","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1002\/art.39117","article-title":"CCR2 expression in neutrophils plays a critical role in their migration into the joints in rheumatoid arthritis","volume":"67","author":"Talbot","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"2024021014340375900_jbmr3388-bib-0040","doi-asserted-by":"crossref","first-page":"13885","DOI":"10.1038\/ncomms13885","article-title":"Osteoblasts secrete Cxcl9 to regulate angiogenesis in bone","volume":"7","author":"Huang","year":"2016","journal-title":"Nat Commun"},{"issue":"7492","key":"2024021014340375900_jbmr3388-bib-0041","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature13145","article-title":"Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone","volume":"507","author":"Kusumbe","year":"2014","journal-title":"Nature"},{"issue":"11","key":"2024021014340375900_jbmr3388-bib-0042","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1038\/nm.3668","article-title":"PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis","volume":"20","author":"Xie","year":"2014","journal-title":"Nat Med"},{"issue":"7","key":"2024021014340375900_jbmr3388-bib-0043","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/nrrheum.2012.80","article-title":"Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis","volume":"8","author":"Mapp","year":"2012","journal-title":"Nat Rev Rheumatol"},{"issue":"5","key":"2024021014340375900_jbmr3388-bib-0044","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1002\/jbmr.2828","article-title":"Targeting VEGF and its receptors for the treatment of osteoarthritis and associated pain","volume":"31","author":"Hamilton","year":"2016","journal-title":"J Bone Miner Res"},{"issue":"6","key":"2024021014340375900_jbmr3388-bib-0045","doi-asserted-by":"crossref","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"},{"issue":"9","key":"2024021014340375900_jbmr3388-bib-0046","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1136\/annrheumdis-2015-207923","article-title":"Halofuginone attenuates osteoarthritis by inhibition of TGF-beta activity and H-type vessel formation in subchondral bone","volume":"75","author":"Cui","year":"2016","journal-title":"Ann Rheum Dis"},{"issue":"7492","key":"2024021014340375900_jbmr3388-bib-0047","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature13146","article-title":"Endothelial Notch activity promotes angiogenesis and osteogenesis in bone","volume":"507","author":"Ramasamy","year":"2014","journal-title":"Nature"},{"issue":"15","key":"2024021014340375900_jbmr3388-bib-0048","doi-asserted-by":"crossref","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"},{"issue":"9","key":"2024021014340375900_jbmr3388-bib-0049","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1136\/annrheumdis-2013-203231","article-title":"Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits mTORC1 signalling and delays surgically induced osteoarthritis in comparison with wild-type mice","volume":"73","author":"Huang","year":"2014","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"2024021014340375900_jbmr3388-bib-0050","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cell.2017.03.035","article-title":"mTOR signaling in growth, metabolism, and disease","volume":"169","author":"Saxton","year":"2017","journal-title":"Cell"},{"issue":"12","key":"2024021014340375900_jbmr3388-bib-0051","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1016\/j.joca.2015.07.012","article-title":"Bone turnover and articular cartilage differences localized to subchondral cysts in knees with advanced osteoarthritis","volume":"23","author":"Chen","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"issue":"9463","key":"2024021014340375900_jbmr3388-bib-0052","first-page":"965","article-title":"ohmander LS","volume":"365","author":"Dieppe","year":"2005","journal-title":"Pathogenesis and management of pain in osteoarthritis. Lancet"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.3388","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/33\/5\/909\/56651046\/jbmr3388.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/33\/5\/909\/56651046\/jbmr3388.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T11:01:07Z","timestamp":1710327667000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/33\/5\/909-920\/7605408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,12]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,1,12]]},"published-print":{"date-parts":[[2018,5,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.3388","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,5,1]]},"published":{"date-parts":[[2018,1,12]]},"assertion":[{"value":"2017-08-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}