Wang Bingjie, Ni Jinghuai, Yu Lingling, Chen Shuai, Shang Wenbin, Fang Penghua, Min Wen
Department of Bone Injury of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Mol Cell Endocrinol. 2025 Apr 1;599:112465. doi: 10.1016/j.mce.2025.112465. Epub 2025 Jan 21.
Chemerin, an adipocyte-secreted adipokine, can regulate bone resorption and bone formation and is a promising therapy for postmenopausal osteoporosis. However, the effect of endogenous chemerin on intraosseous vascular remodeling in postmenopausal osteoporosis remains unclear. In this study, we investigated the effect of chemerin on osteogenesis formation and intraosseous vascular remodeling in ovariectomized Rarres2 knockout (Rarres2) mice. The results showed that the bone mineral density (BMD) and volume score, trabecular thickness, cortical thickness, bone formation marker BALP and osteocalcin, and angiogenesis markers CD31 and EMCN significantly increased in ovariectomized Rarres2 mice. Furthermore, the expression of biomarkers to osteoblasts (β-catenin and Runx2) and angiogenesis markers (VEGF-A, Noggin, and Ang-1) significantly increased in the bone tissue of ovariectomized Rarres2 mice, as well as in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2 mice. Conversely, treatment with chemerin significantly inhibited expression of biomarkers for osteoblasts and angiogenesis markers in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2 mice. More importantly, the supernatants of the primary intraosseous vascular endothelial cells of the Rarres2 mice could promote the osteogenic differentiation effect of BMSCs, which could be blocked by treating with the chemerin recombinant protein. These data indicate that endogenous chemerin has an inhibitory effect on intraosseous vascular formation as well as osteoblast differentiation and proliferation in ovariectomy-induced osteoporosis mice. Chemerin effectively promoted postmenopausal osteoporosis development, which is associated with the involvement of chemerin in the reduction of microcirculation within the skeleton.
瑞仕芬（chemerin）是一种由脂肪细胞分泌的脂肪因子，可调节骨吸收和骨形成，是治疗绝经后骨质疏松症的一种很有前景的疗法。然而，内源性瑞仕芬对绝经后骨质疏松症骨内血管重塑的影响尚不清楚。在本研究中，我们研究了瑞仕芬对去卵巢的视黄酸受体应答蛋白2基因敲除（Rarres2）小鼠成骨形成和骨内血管重塑的影响。结果显示，去卵巢的Rarres2小鼠的骨矿物质密度（BMD）、体积分数、小梁厚度、皮质厚度、骨形成标志物碱性磷酸酶（BALP）和骨钙素，以及血管生成标志物CD31和内皮微管蛋白（EMCN）显著增加。此外，去卵巢的Rarres2小鼠骨组织中，以及Rarres2小鼠的骨髓基质细胞和原发性骨内血管内皮细胞中，成骨细胞生物标志物（β-连环蛋白和Runx2）和血管生成标志物（血管内皮生长因子A（VEGF-A）、头蛋白（Noggin）和血管生成素-1（Ang-1））的表达显著增加。相反，用瑞仕芬处理可显著抑制Rarres2小鼠骨髓基质细胞和原发性骨内血管内皮细胞中成骨细胞生物标志物和血管生成标志物的表达。更重要的是，Rarres2小鼠原发性骨内血管内皮细胞的上清液可促进骨髓间充质干细胞（BMSC）的成骨分化作用，而用瑞仕芬重组蛋白处理可阻断这种作用。这些数据表明，内源性瑞仕芬对去卵巢诱导的骨质疏松症小鼠的骨内血管形成以及成骨细胞分化和增殖具有抑制作用。瑞仕芬有效促进绝经后骨质疏松症的发展，这与瑞仕芬参与骨骼内微循环减少有关。
