Chemerin, a secreted protein mainly produced by adipocytes and hepatocytes, plays a variety of roles in endocrine or paracrine signaling. As reported in human epidemiology, chemerin was correlated with osteoporosis. And the previous in vitro study found that chemerin knockdown promoted osteogenesis and inhibited adipogenesis. However, the function of chemerin in bone metabolism and the underlying mechanism remains unclear. In this study, we uncovered the in vivo function of chemerin in bone homeostasis. We discovered that in obese mice, chemerin was increased in serum, while decreased in the bone marrow; and the chemerin expression in bone tissue was positively correlated with osteogenic genes. To further investigate the function of chemerin in bone metabolism, we generated chemerin deficiency and overexpression mice. We found bone mass and osteogenesis were decreased in chemerin deficiency mice, while were increased in chemerin overexpression mice. Furthermore, we observed that the chemerin expression increased during osteogenic differentiation of MSCs. Besides, we verified that chemerin promoted osteogenic differentiation in C3H10T1/2 cells and BMSCs through Akt/Gsk3β/β‐catenin axis. Treatment with Akt inhibitor (MK2206) abolished the promoting effect of chemerin on osteogenic differentiation and active β‐catenin. Together, our results suggest chemerin in bone marrow, not in serum, promotes osteogenic differentiation and bone formation via Akt/Gsk3β/β‐catenin axis. Chemerin may serve as a therapeutic strategy for osteoporosis.

中文翻译：

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位于骨髓中的Chemerin通过Akt/Gsk3β/β-catenin轴促进小鼠成骨分化和骨形成

Chemerin 是一种主要由脂肪细胞和肝细胞产生的分泌蛋白，在内分泌或旁分泌信号传导中发挥多种作用。正如人类流行病学报告的那样，凯莫瑞与骨质疏松症相关。并且之前的体外研究发现chemerin敲低促进成骨并抑制脂肪生成。然而，chemerin在骨代谢中的作用及其潜在机制尚不清楚。在这项研究中，我们揭示了凯莫瑞在骨稳态中的体内功能。我们发现在肥胖小鼠中，血清中chemerin增加，而骨髓中chemerin减少；并且骨组织中chemerin的表达与成骨基因呈正相关。为了进一步研究 chemerin 在骨代谢中的功能，我们生成了 chemerin 缺乏和过表达小鼠。我们发现 chemerin 缺乏小鼠的骨量和成骨减少，而 chemerin 过表达小鼠的骨量和骨生成增加。此外，我们观察到 chemerin 表达在 MSCs 的成骨分化过程中增加。此外，我们证实chemerin通过Akt/Gsk3β/β-catenin轴促进C3H10T1/2细胞和BMSCs的成骨分化。Akt 抑制剂 (MK2206) 处理消除了凯莫瑞对成骨分化和活性 β-连环蛋白的促进作用。总之，我们的结果表明，骨髓中的凯莫瑞（而非血清）通过 Akt/Gsk3β/β-catenin 轴促进成骨分化和骨形成。Chemerin 可作为骨质疏松症的治疗策略。我们观察到 chemerin 表达在 MSCs 的成骨分化过程中增加。此外，我们证实chemerin通过Akt/Gsk3β/β-catenin轴促进C3H10T1/2细胞和BMSCs的成骨分化。Akt 抑制剂 (MK2206) 处理消除了凯莫瑞对成骨分化和活性 β-连环蛋白的促进作用。总之，我们的结果表明，骨髓中的凯莫瑞（而非血清）通过 Akt/Gsk3β/β-catenin 轴促进成骨分化和骨形成。Chemerin 可作为骨质疏松症的治疗策略。我们观察到 chemerin 表达在 MSCs 的成骨分化过程中增加。此外，我们证实chemerin通过Akt/Gsk3β/β-catenin轴促进C3H10T1/2细胞和BMSCs的成骨分化。Akt 抑制剂 (MK2206) 处理消除了凯莫瑞对成骨分化和活性 β-连环蛋白的促进作用。总之，我们的结果表明，骨髓中的凯莫瑞（而非血清）通过 Akt/Gsk3β/β-catenin 轴促进成骨分化和骨形成。Chemerin 可作为骨质疏松症的治疗策略。Akt 抑制剂 (MK2206) 处理消除了凯莫瑞对成骨分化和活性 β-连环蛋白的促进作用。总之，我们的结果表明，骨髓中的凯莫瑞（而非血清）通过 Akt/Gsk3β/β-catenin 轴促进成骨分化和骨形成。Chemerin 可作为骨质疏松症的治疗策略。Akt 抑制剂 (MK2206) 处理消除了凯莫瑞对成骨分化和活性 β-连环蛋白的促进作用。总之，我们的结果表明，骨髓中的凯莫瑞（而非血清）通过 Akt/Gsk3β/β-catenin 轴促进成骨分化和骨形成。Chemerin 可作为骨质疏松症的治疗策略。