Pro-Angiogenic and Osteogenic Effects of Adipose Tissue-Derived Pericytes Synergistically Enhanced by Nel-like Protein-1
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 osteonecrosi...
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doaj-7494499e3ca649bc851a74511a08da622021-09-25T23:52:08ZengMDPI AGCells2073-44092021-08-01102244224410.3390/cells10092244Pro-Angiogenic and Osteogenic Effects of Adipose Tissue-Derived Pericytes Synergistically Enhanced by Nel-like Protein-1Hyun-Ju An0Kyung Rae Ko1Minjung Baek2Yoonhui Jeong3Hyeon Hae Lee4Hyungkyung Kim5Do Kyung Kim6So-Young Lee7Soonchul Lee8Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 06351, KoreaDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University, College of Medicine, 892 Dongnam-Ro, Gangdong-gu, Seoul 05278, KoreaCHA Graduate School of Medicine, 120 Hyeryong-Ro, Pocheon-si 11160, Gyeonggi-do, KoreaDepartment of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-Ro, Seongnam-si 13496, Gyeonggi-do, KoreaAn 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.https://www.mdpi.com/2073-4409/10/9/2244pericytes<i>Nel</i>-like protein-1angiogenesisbone regenerationbone formationosteonecrosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hyun-Ju An Kyung Rae Ko Minjung Baek Yoonhui Jeong Hyeon Hae Lee Hyungkyung Kim Do Kyung Kim So-Young Lee Soonchul Lee |
spellingShingle |
Hyun-Ju An Kyung Rae Ko Minjung Baek Yoonhui Jeong Hyeon Hae Lee Hyungkyung Kim Do Kyung Kim So-Young Lee Soonchul Lee Pro-Angiogenic and Osteogenic Effects of Adipose Tissue-Derived Pericytes Synergistically Enhanced by Nel-like Protein-1 Cells pericytes <i>Nel</i>-like protein-1 angiogenesis bone regeneration bone formation osteonecrosis |
author_facet |
Hyun-Ju An Kyung Rae Ko Minjung Baek Yoonhui Jeong Hyeon Hae Lee Hyungkyung Kim Do Kyung Kim So-Young Lee Soonchul Lee |
author_sort |
Hyun-Ju An |
title |
Pro-Angiogenic and Osteogenic Effects of Adipose Tissue-Derived Pericytes Synergistically Enhanced by Nel-like Protein-1 |
title_short |
Pro-Angiogenic and Osteogenic Effects of Adipose Tissue-Derived Pericytes Synergistically Enhanced by Nel-like Protein-1 |
title_full |
Pro-Angiogenic and Osteogenic Effects of Adipose Tissue-Derived Pericytes Synergistically Enhanced by Nel-like Protein-1 |
title_fullStr |
Pro-Angiogenic and Osteogenic Effects of Adipose Tissue-Derived Pericytes Synergistically Enhanced by Nel-like Protein-1 |
title_full_unstemmed |
Pro-Angiogenic and Osteogenic Effects of Adipose Tissue-Derived Pericytes Synergistically Enhanced by Nel-like Protein-1 |
title_sort |
pro-angiogenic and osteogenic effects of adipose tissue-derived pericytes synergistically enhanced by nel-like protein-1 |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2021-08-01 |
description |
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. |
topic |
pericytes <i>Nel</i>-like protein-1 angiogenesis bone regeneration bone formation osteonecrosis |
url |
https://www.mdpi.com/2073-4409/10/9/2244 |
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