PDGF-BB prevents destructive repair and promotes reparative osteogenesis of steroid-associated osteonecrosis of the femoral head in rabbits
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摘要Destructive repair characterized by inadequate angiogenesis and osteogenesis is the main pathological progression in steroid-associated osteonecrosis of the femoral head (SONFH). Platelet-derived growth factor-BB (PDGF-BB) is an "angiogenesis and osteogenesis coupling" factor that has been used for the treatment of bone defects in clinic. This study was designed to analyze the ability of PDGF-BB for preventing destructive repair and promoting reparative osteogenesis in SONFH. Steroid-associated osteonecrosis (SAON) was induced and triggered destructive repair of the femoral head by repeated lipopolysaccharide (LPS) and methylprednisolone (MPS) injections in rabbits. At 2, 4, and 6 weeks after induction, recombinant human PDGF-BB, neutralizing PDGF-BB antibody, or saline was intramedullary injected into the proximal femora. At week 6 after SAON induction, the proximal femora were dissected for bone architecture and histological analysis. C3H10T1/2 cells and HUVECs were used for further mechanistic investigation. After PDGF-BB treatment, type H vessels and leptin receptor-positive (LepR+) mesenchymal stem cells (MSCs) increased in the affected femoral head, and more osteoblastic osteogenesis along the bone surfaces but scattered adipocytes in bone marrow tissue than that in the SAON group. PDGF-BB treatment prevented destructive repair progression and led to 50-70 % of osteonecrotic femoral heads undergoing reparative osteogenesis. In particular, we found that PDGF-BB could mediate MSC self-renewal and maintain their osteogenic potency by activating PDGFR/Akt/GSK3β/CERB signaling in the presence of steroids. Moreover, PDGF-BB also stabled the newly formed vascular tubes by recruiting MSCs for improving intraosseous vascular integration. PDGF-BB may be a candidate for the promotion of reparative osteogenesis in SONFH.
出版社接受日期10.12.2022
著者Huijuan Cao, Keda Shi, Jing Long, Yanzhi Liu, Lingli Li, Tianluo Ye, Cuishan Huang, Yuxiao Lai, Xueling Bai, Ling Qin, Xinluan Wang
期刊名稱BONE
出版年份2023
月份2
卷號167
出版社Elsevier
文章號碼116645
國際標準期刊號8756-3282
電子國際標準期刊號1873-2763
語言美式英語
關鍵詞PDGF-BB, Osteonecrosis, Destructive repair, Reparative osteogenesis
