Adipsin promotes bone marrow adiposity by priming mesenchymal stem cells

• DOI: 10.7554/elife.69209
• Publication Date: 2021-06-22T00:00:32Z
• Authors: Nicole Aaron; Michael J Kraakman; Qiuzhong Zhou; Qiongming Liu; Samantha Costa; Jing Yang; Longhua Liu; Lexiang Yu; Liheng Wang; Ying He; Lihong Fan; Hiroyuki Hirakawa; Lei Ding; James Lo; Weidong Wang; Baohong Zhao; Edward Guo; Lei Sun; Cliff J Rosen; Li Qiang
• Keywords: Bone remodeling

Background: Marrow adipose tissue (MAT) has been shown to be vital for regulating metabolism and maintaining skeletal homeostasis in the bone marrow (BM) niche. As a reflection of BM remodeling, MAT is highly responsive nutrient fluctuations, hormonal changes, metabolic disturbances such as obesity diabetes mellitus. Expansion also strongly associated with loss mice humans. However, regulation plasticity remains poorly understood, does mechanism that links changes adiposity remodeling. Methods: We studied deletion Adipsin, its downstream effector, C3, C57BL/6 well bone-protected PPARγ constitutive deacetylation 2KR assess plasticity. The were challenged thiazolidinedione treatment, calorie restriction, or aging induce expansion. Analysis mineral density was performed using μCT scanner by RNA analysis adipocyte osteoblast markers. For vitro studies, primary stromal cells isolated subjected osteoblastogenic adipogenic differentiation chemical treatment followed morphological molecular analyses. Clinical data obtained from samples previous clinical trial fasting high-calorie diet healthy human volunteers. Results: show Adipsin most upregulated adipokine during expansion humans acetylation-dependent manner. Genetic ablation specifically inhibited but not peripheral depots, improved mass aging. These effects mediated through complement component prime common progenitor toward adipogenesis rather than osteoblastogenesis inhibiting Wnt/β-catenin signaling. Conclusions: promotes new formation affects remodeling Our study reveals novel whereby sustains own paracrine endocrine actions unique adipokine. Funding: This work supported National Institutes Health T32DK007328 (NA), F31DK124926 R01DK121140 (JCL), R01AR068970 (BZ), R01AR071463 R01DK112943 (LQ), R24DK092759 (CJR), P01HL087123 (LQ).