Department of Orthopedics and Traumatology, Longyan First Hospital, Longyan, 364000, P. R. China.
Department of Orthopedic Surgery, Fuzhou Second Hospital, Fuzhou, 350007, P. R. China.
Endocrine. 2019 Mar;63(3):639-650. doi: 10.1007/s12020-018-1803-1. Epub 2018 Nov 14.
Osteoporosis is a condition characterized by decreased bone density and bone strength, commonly observed among older individuals. Caveolin-3 (CAV3) is a principal structural protein of the caveolae membrane domains, which has been reported to participate in cell signaling as well as the maintenance of cell structure. The aim of the current study was to investigate the effects involved with the silencing of CAV3 on bone formation among osteoporotic rat models via the Wnt signaling pathway.
Osteoporosis was initially induced by means of ovariotomy among rat models in order to determine the expression of CAV3. Then, to confirm the specific function and mechanism of CAV3 from an osteoporosis perspective, the CAV3 expression vector was constructed and transfected into the osteoblasts of the osteoporotic rats. Afterward, the mRNA and protein expressions of CAV3, β-catenin, low-density lipoprotein receptor-related protein 5 (LRP5), T-cell factor (TCF), and Wnt3a in addition to cell proliferation and apoptosis were detected accordingly.
Positive expression of CAV3 exhibited diminished levels in the bone tissues of osteoporotic rats. The osteoblasts of the osteoporotic rats treated with overexpressed CAV3 displayed elevated mRNA and protein expression levels of β-catenin, LRP5, TCF, and Wnt3a. Increased cell proliferation and decreased cell apoptosis were also observed, while the osteoblasts of the osteoporotic rats treated with si-CAV3 exhibited an opposite result.
Overexpressed CAV3 promotes bone formation and suppresses the osteoporosis progression via the activation of the Wnt signaling in rat models, suggesting CAV3 as a potential target biomarker in the treatment of osteoporosis.
骨质疏松症是一种以骨密度和骨强度降低为特征的疾病，常见于老年人。窖蛋白-3（CAV3）是小窝膜域的主要结构蛋白，据报道它参与细胞信号转导以及细胞结构的维持。本研究旨在通过 Wnt 信号通路研究沉默 CAV3 对骨质疏松症大鼠模型骨形成的影响。
首先通过卵巢切除术诱导大鼠骨质疏松症模型，以确定 CAV3 的表达情况。然后，为了从骨质疏松症的角度证实 CAV3 的具体功能和机制，构建了 CAV3 表达载体并转染到骨质疏松症大鼠的成骨细胞中。随后，检测 CAV3、β-连环蛋白、低密度脂蛋白受体相关蛋白 5（LRP5）、T 细胞因子（TCF）和 Wnt3a 的 mRNA 和蛋白表达以及细胞增殖和凋亡情况。
骨质疏松症大鼠骨组织中 CAV3 的阳性表达水平降低。过表达 CAV3 的骨质疏松症大鼠成骨细胞的β-连环蛋白、LRP5、TCF 和 Wnt3a 的 mRNA 和蛋白表达水平升高。细胞增殖增加，细胞凋亡减少，而沉默 CAV3 的骨质疏松症大鼠成骨细胞则呈现相反的结果。
过表达的 CAV3 通过激活大鼠模型中的 Wnt 信号通路促进骨形成并抑制骨质疏松症的进展，提示 CAV3 可作为骨质疏松症治疗的潜在靶标生物标志物。
