{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:47:29Z","timestamp":1773272849901,"version":"3.50.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"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":[[2004,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ischemic injury to the immature femoral head produces epiphyseal cartilage damage and cessation of endochondral ossification. This study suggests that VEGF facilitates the repair of the necrotic epiphyseal cartilage, which is essential for restoration of endochondral ossification and re-establishment of the growth of the immature femoral head after ischemic necrosis.<\/jats:p>\n               <jats:p>Introduction: Legg-Calve-Perthes disease (LCPD) is a childhood form of osteonecrosis that produces growth arrest of the secondary center of ossification. The cessation of growth is caused by ischemic damage to the hypertrophic zone of the epiphyseal cartilage where endochondral ossification normally occurs. The role of vascular endothelial growth factor (VEGF) in restoring endochondral ossification in the epiphyseal cartilage after ischemic necrosis was investigated in a piglet model of LCPD because the resumption of normal growth is important for maintaining the spherical shape of the femoral head.<\/jats:p>\n               <jats:p>Materials and Methods: Piglet femoral heads were assessed 24 h to 8 weeks after the surgical induction of ischemia. Western blot analysis, ribonuclease protection assay (RPA), immunohistochemistry, and in situ hybridization were performed.<\/jats:p>\n               <jats:p>Results: Western blot analysis and RPA showed increased VEGF protein and mRNA expression, respectively, in the epiphyseal cartilage of the infarcted heads compared with the contralateral normal heads. In the normal femoral heads, VEGF-immunoreactivity (VEGF-IR) and transcripts were observed in the hypertrophic zone of the epiphyseal cartilage. In the infarcted heads, VEGF-IR and transcripts were no longer observed in the hypertrophic zone because of diffuse cell death in that zone from ischemia. However, VEGF-IR and transcripts were observed in the proliferative zone above the necrotic hypertrophic zone. At 8 weeks, vascular granulation tissue invasion of the necrotic hypertrophic zone was observed with active resorption of the necrotic cartilage. In some areas where the necrotic cartilage was completely resorbed, restoration of endochondral ossification was observed. In these areas, VEGF transcripts were observed in the newly formed hypertrophic zone.<\/jats:p>\n               <jats:p>Conclusions: VEGF expression was increased, and its spatial expression was altered in the epiphyseal cartilage after ischemic necrosis of the immature femoral head. VEGF upregulation in the proliferative zone after ischemic damage may play a role in stimulating vascular invasion and granulation tissue formation in the necrotic hypertrophic zone of the epiphyseal cartilage. This may be an important step toward facilitating the resorption of the necrotic cartilage and restoration of endochondral ossification leading to further growth and development of the femoral head.<\/jats:p>","DOI":"10.1359\/jbmr.040911","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T06:05:46Z","timestamp":1146117946000},"page":"2041-2048","source":"Crossref","is-referenced-by-count":42,"title":["Increased VEGF Expression in the Epiphyseal Cartilage After Ischemic Necrosis of the Capital Femoral Epiphysis"],"prefix":"10.1093","volume":"19","author":[{"given":"Harry KW","family":"Kim","sequence":"first","affiliation":[{"name":"Center for Research in Skeletal Development and Pediatric Orthopaedics, Shriners Hospitals for Children, Tampa, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haikuo","family":"Bian","sequence":"additional","affiliation":[{"name":"Center for Research in Skeletal Development and Pediatric Orthopaedics, Shriners Hospitals for Children, Tampa, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Randall","sequence":"additional","affiliation":[{"name":"Center for Research in Skeletal Development and Pediatric Orthopaedics, Shriners Hospitals for Children, Tampa, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Garces","sequence":"additional","affiliation":[{"name":"Center for Research in Skeletal Development and Pediatric Orthopaedics, Shriners Hospitals for Children, Tampa, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis C","family":"Gerstenfeld","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Boston University Medical Center, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A","family":"Einhorn","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Boston University Medical Center, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019182523900_bib1","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1056\/NEJM196611032751804","article-title":"Incidence of Legg-Perthes disease (osteochondritis deformans)","volume":"275","author":"Molloy","year":"1966","journal-title":"N Engl J Med"},{"key":"2024013019182523900_bib2","doi-asserted-by":"crossref","first-page":"860","DOI":"10.2106\/00004623-198466060-00006","article-title":"A long-term follow-up of Legg-Calve-Perthes disease","volume":"66","author":"McAndrew","year":"1984","journal-title":"J Bone Joint Surg Am"},{"key":"2024013019182523900_bib3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/00003086-198007000-00019","article-title":"Methods of measuring in Legg-Calve-Perthes disease with special regard to the prognosis","volume":"150","author":"Mose","year":"1980","journal-title":"Clin Orthop"},{"key":"2024013019182523900_bib4","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.2106\/00004623-198163070-00006","article-title":"The natural history of Legg-Calve-Perthes disease","volume":"63","author":"Stulberg","year":"1981","journal-title":"J Bone Joint Surg Am"},{"key":"2024013019182523900_bib5","first-page":"488","volume-title":"Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism","author":"Whyte","year":"2003","edition":"5th ed."},{"key":"2024013019182523900_bib6","first-page":"951","volume-title":"Lovell and Winter's Pediatric Orthopaedics","author":"Weinstein","year":"1996","edition":"4th ed."},{"key":"2024013019182523900_bib7","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/jor.1100090303","article-title":"Ischemic necrosis of cartilage in spontaneous and experimental lesions of osteochondrosis","volume":"9","author":"Carlson","year":"1991","journal-title":"J Orthop Res"},{"key":"2024013019182523900_bib8","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1302\/0301-620X.48B4.793","article-title":"The nutrition of immature joint cartilage in the lamb","volume":"48","author":"McKibbin","year":"1966","journal-title":"J Bone Joint Surg Br"},{"key":"2024013019182523900_bib9","doi-asserted-by":"crossref","first-page":"688","DOI":"10.2106\/00004623-200105000-00007","article-title":"Histopathologic changes in growth-plate cartilage following ischemic necrosis of the capital femoral epiphysis. 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