PGC-1α Controls Skeletal Stem Cell Fate and Bone-Fat Balance in Osteoporosis and Skeletal Aging by Inducing TAZ

Abstract

Aberrant lineage specification of skeletal stem cells (SSCs) contributes to reduced bone mass and increased marrow adipose tissue (MAT) in osteoporosis and skeletal aging. Although master regulators of osteoblastic and adipogenic lineages have been identified, little is known about factors that are associated with MAT accumulation and osteoporotic bone loss. Here, we identify peroxisome-proliferator-activated receptor γ coactivator 1-α (PGC-1α) as a critical switch of cell fate decisions whose expression decreases with aging in human and mouse SSCs. Loss of PGC-1α promoted adipogenic differentiation of murine SSCs at the expense of osteoblastic differentiation. Deletion of PGC-1α in SSCs impaired bone formation and indirectly promoted bone resorption while enhancing MAT accumulation. Conversely, induction of PGC-1α attenuated osteoporotic bone loss and MAT accumulation. Mechanistically, PGC-1α maintains bone and fat balance by inducing TAZ. Our results suggest that PGC-1α is a potentially important therapeutic target in the treatment of osteoporosis and skeletal aging.

Sensory nerves regulate mesenchymal stromal cell lineage commitment by tuning sympathetic tones

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Flufenamic Acid Inhibits Adipogenic Differentiation of Mesenchymal Stem Cells by Antagonizing the PI3K/AKT Signaling Pathway

“…0.5 to 1 mm distal to the proximal epiphysis in the trabecular region of the femurs were chosen to analyse the parameters of adipocyte according to guidelines set by the American Society for Bone and Mineral Research (ASBMR) [26]. Adipocyte numbers and area per tissue area were analyzed on H&E staining images using SPOT5.3 Microscopy Imaging Software [27]. (Figure 1(c)) and CEBPA (Figure 1(d)) at day 14, whereas FFA at 200 μM did not.…”

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“…Age‐related bone loss made the risk of fractures among elderly individuals raised, which is believed to occur due to lessened bone formation and enhanced marrow fat accumulation . BMSC have the ability of differentiating into variety of cells, including osteoblasts and adipocytes .…”