Abstract
Osteoporosis is a chronic age-related disease. During aging, bone marrow-derived mesenchymal stem cells (BMSCs) display increased adipogenic, along with decreased osteogenic, differentiation capacity. The aim of the present study was to investigate the effect of calcitonin gene-related peptide (CGRP) on the osteogenic and adipogenic differentiation potential of BMSC-derived osteoblasts. Here, we found that the level of CGRP was markedly lower in bone marrow supernatant from aged mice compared with that in young mice. In vitro experiments indicated that CGRP promoted the osteogenic differentiation of BMSCs while inhibiting their adipogenic differentiation. Compared with vehicle-treated controls, aged mice treated with CGRP showed a substantial promotion of bone formation and a reduction in fat accumulation in the bone marrow. Similarly, we found that CGRP could significantly enhance bone formation in ovariectomized (OVX) mice in vivo. Together, our results suggested that CGRP may be a key regulator of the age-related switch between osteogenesis and adipogenesis in BMSCs and may represent a potential therapeutic strategy for the treatment of age-related bone loss.
Highlights
Osteoporosis is a chronic disease caused by the breakdown of bone homeostasis, with elderly and postmenopausal women being the populations most at risk of developing this condition (NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, 2001; Rachner et al, 2011)
We found that Calcitonin gene-related peptide (CGRP) promotes the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and inhibits their adipogenic differentiation and senescence
Given the vital role of CGRP in bone metabolism (Irie et al, 2002; Schinke et al, 2004; Appelt et al, 2020) and that CGRP has been reported to stimulate the proliferation and osteogenic differentiation of rat-derived BMSCs (Liang et al, 2015), we subsequently hypothesized that CGRP may be involved in regulating BMSC functions during the aging process in mice
Summary
Osteoporosis is a chronic disease caused by the breakdown of bone homeostasis, with elderly and postmenopausal women being the populations most at risk of developing this condition (NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, 2001; Rachner et al, 2011). Age-related bone loss and osteoporosis have been associated with reduced numbers of osteoblasts and increased numbers of adipocytes (Idris et al, 2009; Yu and Wang, 2016). Bone homeostasis depends on the balance between the osteogenic and adipogenic differentiation of BMSCs Age-related osteoporosis results from reduced osteogenic differentiation and increased adipogenic differentiation of BMSCs in elderly patients (Shen et al, 2012; Childs et al, 2015; Li et al, 2017). CGRP exists as two isoforms—α-CGRP and β-CGRP—which are encoded by the CALCA and CALCB genes, respectively. In mice, the Calca gene has been shown to affect bone remodeling; the underlying mechanism remains unclear (Schinke et al, 2004)
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