Bone-derived sclerostin and Wnt/β-catenin signaling regulate PDGFRα + adipoprogenitor cell differentiation.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The Wnt signaling antagonist, sclerostin, is a potent suppressor of bone acquisition that also mediates endocrine communication between bone and adipose. As a result, Sost -/- mice exhibit dramatic increases in bone formation but marked decreases in visceral and subcutaneous adipose that are secondary to alterations in lipid synthesis and utilization. While interrogating the mechanism by which sclerostin influences adipocyte metabolism, we observed paradoxical increases in the adipogenic potential and numbers of CD45 - :Sca1 + :PDGFRα + adipoprogenitors in the stromal vascular compartment of fat pads isolated from male Sost -/- mice. Lineage tracing studies indicated that sclerostin deficiency blocks the differentiation of PDGFRα + adipoprogenitors to mature adipocytes in association with increased Wnt/β-catenin signaling. Importantly, osteoblast/osteocyte-specific Sost gene deletion mirrors the accumulation of PDGFRα + adipoprogenitors, reduction in fat mass, and improved glucose metabolism evident in Sost -/- mice. These data indicate that bone-derived sclerostin regulates multiple facets of adipocyte physiology ranging from progenitor cell commitment to anabolic metabolism.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.