{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T16:20:42Z","timestamp":1784218842061,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1I1A1A01073917, 2019R1A2C4070492, 2019R1C1C1004017"],"award-info":[{"award-number":["2020R1I1A1A01073917, 2019R1A2C4070492, 2019R1C1C1004017"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>An important objective of vascularized tissue regeneration is to develop agents for osteonecrosis. We aimed to identify the pro-angiogenic and osteogenic efficacy of adipose tissue-derived (AD) pericytes combined with Nel-like protein-1 (NELL-1) to investigate the therapeutic effects on osteonecrosis. Tube formation and cell migration were assessed to determine the pro-angiogenic efficacy. Vessel formation was evaluated in vivo using the chorioallantoic membrane assay. A mouse model with a 2.5 mm necrotic bone fragment in the femoral shaft was used as a substitute for osteonecrosis in humans. Bone formation was assessed radiographically (plain radiographs, three-dimensional images, and quantitative analyses), and histomorphometric analyses were performed. To identify factors related to the effects of NELL-1, analysis using microarrays, qRT-PCR, and Western blotting was performed. The results for pro-angiogenic efficacy evaluation identified synergistic effects of pericytes and NELL-1 on tube formation, cell migration, and vessel formation. For osteogenic efficacy analysis, the mouse model for osteonecrosis was treated in combination with pericytes and NELL-1, and the results showed maximum bone formation using radiographic images and quantitative analyses, compared with other treatment groups and showed robust bone and vessel formation using histomorphometric analysis. We identified an association between FGF2 and the effects of NELL-1 using array-based analysis. Thus, combinatorial therapy using AD pericytes and NELL-1 may have potential as a novel treatment for osteonecrosis.<\/jats:p>","DOI":"10.3390\/cells10092244","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T11:01:37Z","timestamp":1630321297000},"page":"2244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pro-Angiogenic and Osteogenic Effects of Adipose Tissue-Derived Pericytes Synergistically Enhanced by Nel-like Protein-1"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5359-715X","authenticated-orcid":false,"given":"Hyun-Ju","family":"An","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6164-8674","authenticated-orcid":false,"given":"Kyung Rae","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjung","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonhui","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Hae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0271-2493","authenticated-orcid":false,"given":"Hyungkyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University, College of Medicine, 892 Dongnam-Ro, Gangdong-gu, Seoul 05278, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"CHA Graduate School of Medicine, 120 Hyeryong-Ro, Pocheon-si 11160, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soonchul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ref_1","first-page":"e51312","article-title":"Endothelial cell tube formation assay for the in vitro study of angiogenesis","volume":"91","author":"Henry","year":"2014","journal-title":"JoVE"},{"key":"ref_2","first-page":"102","article-title":"Depot-Based Delivery Systems for Pro-Angiogenic Peptides: A Review","volume":"3","author":"Benoit","year":"2015","journal-title":"Front. 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