Osteogenic effect of bone marrow mesenchymal stem cell-derived exosomes on steroid-induced osteonecrosis of the femoral head

Abstract

BackgroundAnimal studies have demonstrated the therapeutic effect of mesenchymal stem cells (MSCs) on osteogenesis, but little is known about the functions of exosomes (Exos) released by bone MSCs (BMSCs). Here, we investigated the effect of BMSC Exos on steroid-induced femoral head necrosis (SFHN) and explored the vital genes involved in this process.Materials and methodsBMSCs were isolated from healthy and SFHN rats. BMSC Exos were isolated using the Exosome Precipitation Kit and characterized by transmission electron microscopy and Western blotting. SFHN BMSCs were incubated with Exos from healthy BMSCs. Osteogenic ability was assessed by oil red O staining and alizarine red staining. Differentially expressed genes (DEGs) induced by Exos were screened using the Osteogenesis RT2 Profiler PCR Array. The effect of upregulated Sox9 was examined using lentivirus-mediated siRNA.ResultsThe results revealed that BMSC Exos were 100–150 nm in size and expressed CD63. Moreover, BMSC Exo-treated SFHN cells exhibited suppressed adipogenesis compared to model cells. PCR array showed that eleven and nine genes were upregulated and downregulated, respectively, in the BMSC Exo-treated SFHN cells compared to the model group. Among the DEGs, osteogenesis-related genes, including Bmp2, Bmp6, Bmpr1b, Mmp9, and Sox9, may play important roles in SFHN. Furthermore, the DEGs were mainly involved in immune response, osteoblast differentiation, and in the transforming growth factor-β/bone morphogenetic protein signaling pathway. The level of the SOX9 protein was upregulated by Exos, and Sox9 silencing significantly decreased the osteogenic effect of BMSC Exos.ConclusionOur data suggest that Exos derived from BMSCs mainly affect SFHN osteogenesis, and this finding can be further investigated to develop a novel therapeutic agent for SFHN.

MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

“…In addition, Huang et al suggested that Icariin could improve the balance between osteogenic differentiation and adipogenic differentiation of BMSCs and then reduce the bone loss of SANFH rats [36]. These findings indicate that BMSCs are the key cytological basis for the pathogenetic mechanism of SANFH [6]. Therefore, exploring the molecules involved in the process of BMSC differentiation is expected to provide new ideas for the diagnosis and treatment of SANFH.…”

“…including adipocytes, chondrocytes, and osteoblasts [6]. Previous studies demonstrated that the change in osteogenic differentiation of BMSCs is related to SANFH [7,8].…”

Exosomal miR‐130a‐3p regulates osteogenic differentiation of Human Adipose‐Derived stem cells through mediating SIRT7/Wnt/β‐catenin axis

“…The fact that exosomes carry miRNAs which serve as important mediators of intercellular communication, has been proven to promote osteogenic differentiation of stem cells. 4,29,30 MiRNAs play a crucial role in bone development and homoeostasis. 8,31 Our findings revealed that overexpression of miR-130a-3p can promoted osteogenic differentiation but inhibited proliferation of ADSCs.…”

β‐ecdysone promotes osteogenic differentiation of bone marrow mesenchymal stem cells

“…Numerous findings support the notion that the decreased osteogenic differentiation ability of BMSCs is closely related to the pathogenesis of ONFH. 14 A recent study reported that βEcd possesses multiple pharmacological actions, including protection against β-amyloid-induced apoptosis. 15,16 Previously, βEcd was shown to increase the differentiation of mesenchymal progenitor cells towards osteoblasts in vitro, which is consistent with the observation of an increased osteoblast surface following in vivo βEcd treatment.…”