Ontology highlight
ABSTRACT: Objectives
Insulin-like growth factor-binding protein 7 (IGFBP7) is a low-affinity insulin growth factor (IGF) binder that may play an important role in bone metabolism. We previously reported that IGFBP7 enhanced osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) via the Wnt/?-catenin signalling pathway. In this study, we tried to reveal its function in osteoclast differentiation and osteoporosis.Methods
We used both in vitro and in vivo studies to investigate the effects of IGFBP7 on RANKL-induced osteoclastogenesis and osteoporosis, together with the underlying molecular mechanisms of these processes.Results
We show that IGFBP7 inhibited receptor activation of nuclear factor-?B (NF-?B) ligand (RANKL)-induced osteoclastogenesis, F-actin ring formation and bone resorption, which was confirmed by using recombinant IGFBP7 protein, lentivirus and siRNA. The NF-?B signalling pathway was inhibited during this process. Moreover, in a mouse ovariectomy-induced osteoporosis model, IGFBP7 treatment attenuated osteoporotic bone loss by inhibiting osteoclast activity.Conclusions
Taken together, these findings show that IGFBP7 suppressed osteoclastogenesis in vitro and in vivo and suggest that IGFBP7 is a negative regulator of osteoclastogenesis and plays a protective role in osteoporosis. These novel insights into IGFBP7 may facilitate the development of potential treatment strategies for oestrogen deficiency-induced osteoporosis and other osteoclast-related disorders.
SUBMITTER: Ye C
PROVIDER: S-EPMC7046308 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Ye Chenyi C Hou Weiduo W Chen Mo M Lu Jinwei J Chen Erman E Tang Lan L Hang Kai K Ding Qianhai Q Li Yan Y Zhang Wei W He Rongxin R
Cell proliferation 20191230 2
<h4>Objectives</h4>Insulin-like growth factor-binding protein 7 (IGFBP7) is a low-affinity insulin growth factor (IGF) binder that may play an important role in bone metabolism. We previously reported that IGFBP7 enhanced osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) via the Wnt/β-catenin signalling pathway. In this study, we tried to reveal its function in osteoclast differentiation and osteoporosis.<h4>Methods</h4>We used both in vitro and in vivo studies to ...[more]