Adipsin promotes bone marrow adiposity by priming mesenchymal stem cells

Area of Science:

• Endocrinology
• Bone Biology
• Metabolic Research

Background:

• Marrow adipose tissue (MAT) is crucial for bone marrow (BM) metabolism and skeletal homeostasis.
• MAT expansion correlates with bone loss and is sensitive to metabolic changes.
• Mechanisms linking marrow adiposity and bone remodeling are not fully understood.

Purpose of the Study:

• Investigate the role of Adipsin in regulating BM plasticity and bone remodeling.
• Elucidate the mechanism by which Adipsin influences adipogenesis versus osteoblastogenesis.
• Assess Adipsin's impact on bone mass during conditions of bone loss.

Main Methods:

• Studied Adipsin and C3 deletion in mice, including PPARγ 2KR models.
• Induced bone loss and MAT expansion via thiazolidinedione treatment, calorie restriction, and aging.
• Analyzed bone mineral density, marrow adiposity, and gene expression; conducted in vitro differentiation assays.

Main Results:

• Adipsin is upregulated during MAT expansion in mice and humans, dependent on PPARγ acetylation.
• Genetic Adipsin ablation inhibited MAT expansion and preserved bone mass under various bone-loss conditions.
• Adipsin, via C3, promotes progenitor cells towards adipogenesis, inhibiting Wnt/β-catenin signaling.

Conclusions:

• Adipsin promotes adipocyte formation and influences skeletal remodeling within the BM niche.
• Revealed a novel mechanism of BM plasticity regulation through Adipsin's paracrine and endocrine actions.