CXM102 Regulates the Multiple Differentiation and Anti-Inflammation of Human Bone Marrow-Derived Leptin Receptor-Positive Stromal Cells In Vitro

Abstract

Bone marrow-derived leptin receptor-expressing (LepR+) stromal cells (LepR+ BMSCs) have been identified as the primary source of osteoblasts, adipocytes, and fibroblasts in the bone marrow, and they play key roles in the maintenance of the bone marrow microenvironment; however, research on the fate and immunomodulatory changes of human LepR+ BMSCs is limited. Here, we isolated LepR+ BMSCs from a young donor and studied their fate changes of osteogenic, adipogenic, myogenic differentiation, and immunomodulation with or without CXM102, a novel compound that we have previously demonstrated its anti-osteoporotic effects in mice. Our results showed that CXM102 facilitated a preferential lineage shift toward osteogenesis from adipogenesis of LepR+ BMSCs in vitro, as evidenced by increased RUNX 2 expression and decreased PPARγ in a bivalent differentiation system. Moreover, interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were markedly downregulated in HS-5 stromal cells cocultured with conditioned medium from CXM102-treated LepR+ BMSCs. Furthermore, CXM102 also inhibited collagen I deposition in LepR+ BMSCs when induced into myogenesis. These results demonstrated that CXM102 could promote osteogenesis, but inhibit adipogenesis and myogenesis of LepR+ BMSCs, while also showing benign immunomodulation in vitro.