{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:57:18Z","timestamp":1788533838934,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T00:00:00Z","timestamp":1574035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemic damage aggravation of femoral head collapse is a prominent pathologic feature of osteonecrosis of the femoral head (ONFH). In this regard, S100 calcium binding protein A9 (S100A9) is known to deteriorate joint integrity, however, little is understood about which role S100A9 may play in ONFH. In this study, a proteomics analysis has revealed a decrease in the serum S100A9 level in patients with ONFH upon hyperbaric oxygen therapy. Serum S100A9 levels, along with serum vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), and tartrate-resistant acid phosphatase 5b levels were increased in patients with ONFH, whereas serum osteocalcin levels were decreased as compared to healthy controls. Serum S100A9 levels were increased with the Ficat and Arlet stages of ONFH and correlated with the patients with a history of being on glucocorticoid medication and alcohol consumption. Osteonecrotic tissue showed hypovasculature histopathology together with weak immunostaining for vessel marker CD31 and von Willrbrand factor (vWF) as compared to femoral head fracture specimens. Thrombosed vessels, fibrotic tissue, osteocytes, and inflammatory cells displayed strong S100A9 immunoreactivity in osteonecrotic lesion. In vitro, ONFH serum and S100A9 inhibited the tube formation of vessel endothelial cells and vessel outgrowth of rat aortic rings, whereas the antibody blockade of S100A9 improved angiogenic activities. Taken together, increased S100A9 levels are relevant to the development of ONFH. S100A9 appears to provoke avascular damage, ultimately accelerating femoral head deterioration through reducing angiogenesis. This study provides insight into the molecular mechanism underlying the development of ONFH. Here, analysis also highlights that serum S100A9 is a sensitive biochemical indicator of ONFH.<\/jats:p>","DOI":"10.3390\/ijms20225786","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T04:31:10Z","timestamp":1574051470000},"page":"5786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["S100 Calcium Binding Protein A9 Represses Angiogenic Activity and Aggravates Osteonecrosis of the Femoral Head"],"prefix":"10.3390","volume":"20","author":[{"given":"Re-Wen","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Medicine; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Shiung","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Core Laboratory for Phenomics &amp; Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Wen","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Core Laboratory for Phenomics &amp; Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Shan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Core Laboratory for Phenomics &amp; Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jih-Yang","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Core Laboratory for Phenomics &amp; Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,18]]},"reference":[{"key":"ref_1","first-page":"I12178","article-title":"Avascular necrosis of the hip","volume":"365","author":"Lamb","year":"2019","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1302\/0301-620X.101B7.BJJ-2018-1309.R1","article-title":"Pain catastrophizing, anxiety, and depression in hip pathology","volume":"101","author":"Hampton","year":"2019","journal-title":"Bone Jt. 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