{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:33:22Z","timestamp":1760297602868},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The spontaneously hypertensive rat (SHR) is a widely used animal model for the study of hypertension. It also exhibits an osteonecrosis of the femoral epiphysis that resembles the clinical features of Perthes' disease in humans. In this rat model, occlusion of the epiphyseal vessels occurs as a result of a breakdown of the mechanically vulnerable epiphysis. The postnatal development of the epiphysis recapitulates the serial events of the endochondral ossification (i.e., cartilage formation), chondrocyte hypertrophy, cartilage mineralization, vascularization, and introduction of osteoblasts that form the secondary ossification center within the epiphysis. In the present study, a detailed radiographic and histological analysis demonstrates that the osteonecrosis is preceded by a disturbance of the cartilage mineralization and a disturbance of the ossification, despite a normal hypertrophy of the epiphyseal cartilage. These observations suggest that abnormal development of the femoral epiphysis occurs much earlier than manifestation of the osteonecrosis. They lead us to a hypothesis that yet-unclarified transitional events between the cartilage hypertrophy and the cartilage mineralization may be affected in SHRs. Type X collagen is a developmentally regulated matrix molecule that is implicated in the mineralization of the hypertrophied chondrocytes. We show that the expression of type X collagen during epiphyseal ossification is delayed in SHRs (vs. normal controls), suggesting disturbed growth and\/or differentiation of the epiphyseal chondrocytes. Postnatal growth and differentiation of the chondrocytes at least partly depend on insulin-like growth factor-I (IGF-I), which is produced by the chondrocytes in response to the pituitary growth hormone and stimulates cartilage growth in situ. The present study demonstrates an altered IGF-I expression during early postnatal life in SHRs and suggests that the altered IGF-I expression as well as the following delay in upregulation of type X collagen may cause the mechanical vulnerability of the femoral epiphysis in SHRs.<\/jats:p>","DOI":"10.1359\/jbmr.2000.15.1.111","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T01:45:01Z","timestamp":1146102301000},"page":"111-119","source":"Crossref","is-referenced-by-count":16,"title":["Altered Postnatal Expression of Insulin-Like Growth Factor-I (IGF-I) and Type X Collagen Preceding the Perthes' Disease\u2013Like Lesion of a Rat Model"],"prefix":"10.1093","volume":"15","author":[{"given":"Masanori","family":"Kikkawa","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Shiga University of Medical Science, Shiga, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Imai","sequence":"additional","affiliation":[{"name":"Japan Society for the Promotion of Science, Shiga, Japan"},{"name":"Department of Orthopaedic Surgery, Shiga University of Medical Science, Shiga, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinsuke","family":"Hukuda","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Shiga University of Medical Science, Shiga, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024020714111341800_bib1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1253\/jcj.41.259","article-title":"Pathogenesis of spontaneous hypertension as a model for essential hypertension","volume":"41","author":"Yamori","year":"1977","journal-title":"Jpn Circ J"},{"key":"2024020714111341800_bib2","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1253\/jcj.27.282","article-title":"Development of a strain of spontaneously hypertensive rats","volume":"27","author":"Okamoto","year":"1963","journal-title":"Jpn Circ J"},{"key":"2024020714111341800_bib3","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1210\/endo-112-2-562","article-title":"Specificity of the alteration in the aldosterone biosynthesis in the spontaneously hypertensive rat","volume":"112","author":"Braley","year":"1983","journal-title":"Endocrinology"},{"key":"2024020714111341800_bib4","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1210\/endo-98-5-1109","article-title":"Abnormal thyroid function in spontaneously hypertensive rats","volume":"98","author":"Kojima","year":"1976","journal-title":"Endocrinology"},{"key":"2024020714111341800_bib5","doi-asserted-by":"crossref","first-page":"530","DOI":"10.3109\/17453678809148778","article-title":"Osteonecrosis of the femoral head of growing, spontaneously hypertensive rats","volume":"59","author":"Hirano","year":"1988","journal-title":"Acta Orthop Scand"},{"key":"2024020714111341800_bib6","first-page":"31","article-title":"Idiopathic necrosis of the femoral epiphyseal nucleus in rats","volume":"227","author":"Iwasaki","year":"1991","journal-title":"Clin Orthop"},{"key":"2024020714111341800_bib7","doi-asserted-by":"crossref","first-page":"7932","DOI":"10.1073\/pnas.83.20.7932","article-title":"Evidence suggesting that the direct growth promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin","volume":"83","author":"Sclechter","year":"1986","journal-title":"Proc Natl Sci USA"},{"key":"2024020714111341800_bib8","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1126\/science.3523759","article-title":"Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate","volume":"233","author":"Nilsson","year":"1986","journal-title":"Science"},{"key":"2024020714111341800_bib9","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1056\/NEJM198002143020704","article-title":"Somatomedins. 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