Longhua Hospital, China; Spine Institute, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, 200032, China.
Longhua Hospital, China; Spine Institute, China; School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, 200032, China.
J Pharmacol Sci. 2018 Mar;136(3):155-164. doi: 10.1016/j.jphs.2018.01.007. Epub 2018 Feb 10.
Primary osteoporosis (POP), which is caused by unbalanced bone remodeling, leads to significant economic and societal burdens globally. Gushukang (GSK) granule serves as one commonly used prescription for POP in Traditional Chinese Medicine (TCM). The present study aimed to clarify the exact roles of GSK in bone remodeling with in vivo and in vitro assays. Here we showed that GSK prevented bone loss and the alternations of osteoporotic bone parameters as well as the decreased density of osteoclast in ovariectomized (OVX) mice. GSK inhibited receptor activator for nuclear factor-κ B Ligand (RANKL)-activated osteoclastogenesis in bone marrow macrophages (BMMs). At the molecular levels, GSK inhibited the expression of nuclear factor of activated T cells cytoplasm 1(NFATc1) and c-Fos, two master regulators of osteoclastogenesis. GSK also inhibited bone resorbed genetic expression of matrix metalloproteinase 9 (MMP9), cathepsin K (Ctsk), TRAP and carbonic anhydrase II (Car2). Meanwhile, GSK stimulated osteoblastogenesis from bone primary mesenchymal stem cells (MSCs) and enhanced the expression of Osteirx, and Runx2. GSK also stimulated the expression of Col-1, Osteocalcein and alkaline phosphatase (ALP). Our investigation established the systemic bone protective effects of GSK by suppressing osteoclastogenesis and stimulating osteoblastogenesis and laid bases for new drugs discovery in treating POP.
原发性骨质疏松症（POP）是由于骨重建失衡引起的，在全球范围内造成了巨大的经济和社会负担。骨疏康颗粒是中医药治疗 POP 的常用方剂之一。本研究旨在通过体内和体外实验明确骨疏康颗粒在骨重建中的确切作用。结果表明，骨疏康颗粒可预防去卵巢小鼠的骨丢失和骨质疏松骨参数的改变以及破骨细胞密度的降低。骨疏康颗粒抑制核因子κ B 受体激活剂配体（RANKL）激活的破骨细胞生成。在分子水平上，骨疏康颗粒抑制破骨细胞生成的两个主要调节因子核因子活化 T 细胞胞浆 1（NFATc1）和 c-Fos 的表达。骨疏康颗粒还抑制了基质金属蛋白酶 9（MMP9）、组织蛋白酶 K（Ctsk）、TRAP 和碳酸酐酶 II（Car2）的骨吸收基因表达。同时，骨疏康颗粒刺激骨原代间充质干细胞（MSCs）向成骨细胞分化，并增强 Osteirx 和 Runx2 的表达。骨疏康颗粒还刺激 Col-1、骨钙素和碱性磷酸酶（ALP）的表达。本研究通过抑制破骨细胞生成和刺激成骨细胞生成，确立了骨疏康颗粒的系统骨保护作用，为治疗 POP 的新药发现奠定了基础。
