Scara3 regulates bone marrow mesenchymal stem cell fate switch between osteoblasts and adipocytes by promoting Foxo1

Abstract

Objectives Scavenger receptor class A, member 3 (Scara3) was involved in adipogenesis. However, the effect of Scara3 on the switch between osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) remains elusive. Materials and Methods The correlations between SCARA3 with the osteogenic‐related were analysed based on the GTEx database. The effects of Scara3 on osteogenic or adipogenic differentiation of BMSCs were evaluated by qPCR, Western blot (WB) and cell staining. The mechanisms of Scara3 regulating Foxo1 and autophagy were validated by co‐expression analysis, WB and immunofluorescence. In vivo, Scara3 adeno‐associated virus was injected into intra‐bone marrow of the aged mice and ovariectomized (OVX) mice whose phenotypes were confirmed by micro‐CT, calcein double labelling and immunochemistry (HE and OCN staining). Results SCARA3 was positively correlated with osteogenic‐related genes. Scara3 expression gradually decreased during adipogenesis but increased during osteogenesis. Moreover, the deletion of Scara3 favoured adipogenesis over osteogenesis, whereas overexpression of Scara3 significantly enhanced the osteogenesis at the expense of adipogenesis. Mechanistically, Scara3 controlled the cell fate by promoting Foxo1 expression and autophagy flux. In vivo, Scara3 promoted bone formation and reduced bone marrow fat accumulation in OVX mice. In the aged mice, Scara3 overexpression alleviated bone loss as well. Conclusions This study suggested that Scara3 regulated the switch between adipocyte and osteoblast differentiation, which represented a potential therapeutic target for bone loss and osteoporosis.

Morinda officinalis polysaccharide promotes the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells via microRNA-210-3p/scavenger receptor class A member 3

“…38 In OP, it is reported that SCARA3 expression is upregulated during the osteogenesis of hBMSCs and promotes the osteogenic differentiation of hBMSCs by regulating Foxo1 while inhibiting adipogenic differentiation. 39 Our study also found that SCARA3 expression was significantly upregulated in hBMSCs induced by osteogenic differentiation, that additionally, SCARA3 was proven to be a downstream target of miR-210-3p, and that MOP could upregulate SCARA3 expression through repressing miR-210-3p expression.…”

Comprehensive analysis of circRNA expression profiles in postmenopausal women differing in bone mineral density

“…From the bioinformatics analysis, we obtained 57 OP-related target genes of hsa-miR-296-5p, hsa-miR-370, and hsa-miR-635, including fibroblast growth factor receptor 1 (FGFR1), [39] RUNX2, [40] FOXO1, [41] STAT3 [42] and recombinant gremlin 2 (GREM2), [43] all of which have been confirmed to be the key ones. According to the functional enrichment analysis on the related genes predicted by hsa-miR-370, PI3K-alpha (PIK3CA), FOXO1, STAT3 and mitogen-activated protein kinase 8 (MAPK8) were enriched in FoxO signaling pathway and advanced glycosylation end product (AGE) and receptor of advanced glycosylation end product (RAGE) signaling pathway, respectively.…”

IRF4 suppresses osteogenic differentiation of BM-MSCs by transcriptionally activating miR-636/DOCK9 axis

“…reported a positive association between Scara3 and osteogenic differentiation of BM-MSCs. 23 Nevertheless, biomarkers of osteogenic differentiation are still limited.…”