S-nitrosylation and MSC-mediated body composition

Mesenchymal stem cells (MSCs) are nonhematopoietic stromal cells that can differentiate into multiple mesodermal lineages including adipocytes, osteoblasts, chondrocytes and myocytes. Adult stem cell differentiation is controlled by activation of lineagespecific transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ) and Runx2, two key transcription factors that govern differentiation of MSCs into adipocytes and osteoblasts, respectively. An inverse relationship exists between adipogenesis and osteogenesis. With aging, the differentiation balance in the bone marrow shifts from primarily osteogenesis to adipogenesis, underlying age-related bone loss. Thus, as the population ages and osteoporosis becomes more prevalent, it is crucial to understand the mechanisms that govern the balance between adipogenesis and osteogenesis. PPARγ, a ligand-activated nuclear receptor required for adipogenesis, is a prominent transcriptional regulator of the bi-lineage differentiation switch of MSCs. PPARγ heterozygous knockout mice have higher bone volume and enhanced osteogenic differentiation of bone marrow cells compared to wild type (WT), indicating that PPARγ exerts inhibitory effects on osteogenesis [1]. Several transcriptional regulators of PPARγ modulate the bilineage equilibrium of bone marrow MSCs. However, post-translational regulators of PPARγ-mediated lineage bifurcation remain elusive. Nitric Oxide (NO), which regulates diverse biological functions such as vasodilation, also plays an important role in modulating the balance between adipocyte and osteoblast differentiation. We tested the hypothesis that S-nitrosylation, a crucial component of NO signaling, can modify PPARγ activity and hence the balance between adipogenesis and osteogenesis [2] Editorial