腰椎间盘退行性疾病已成为全球严重的卫生问题，但临床缺乏安全有效的药物。我们前期研究发现1）OPG基因敲除小鼠随着增龄软骨终板部位软骨细胞肥大凋亡，破骨细胞形成，椎间盘出现退变。提示OPG对椎间盘具有保护作用，但机制不清楚；2）健腰密骨片及其有效组分淫羊藿苷、齐墩果酸、蛇床子素通过OPG/RANK/RANKL轴抑制破骨细胞形成。因此我们提出“健腰密骨片通过调控软骨细胞OPG/RANK/RANKL轴的表达延缓椎间盘退变”的假说。应用椎间盘退变模型，观察OPG/RANK/RANKL轴的改变；通过软骨细胞与破骨细胞共培养，观察软骨细胞通过该轴调控破骨细胞形成的作用机制；构建软骨细胞特异性OPG敲除小鼠，观察软骨细胞OPG缺失导致软骨终板破骨细胞活跃，椎间盘发生退变的作用；观察健腰密骨片通过调控软骨细胞OPG/RANK/RANKL轴的表达延缓椎间盘退变的药效机制，为椎间盘退变性疾病的防治提供新思路。

Degenerative disease of lumbar intervertebral disc has become a serious health problem in the world, but there is a lack of safe and effective drugs in clinic. Our previous study found that chondrocyte hypertrophy apoptosis, osteoclast formation and intervertebral disc degeneration in the cartilage endplate of OPG gene knockout mice with age increasing. The results suggest that OPG has protective role on intervertebral disc, but the mechanism is unclear; Jian Yao Mi Gu Pian and its effective components icariin, oleanolic acid and osthol inhibit osteoclast formation through OPG/RANK/RANKL axis. Therefore, we put forward the hypothesis that "Jian Yao Mi Gu Pian delays intervertebral disc degeneration by regulating the expression of OPG/RANK/RANKL axis of chondrocytes". The changes of OPG/RANK/RANKL axis will be observed in intervertebral disc degeneration model, the mechanism of chondrocytes regulating osteoclast formation through co-culture of chondrocytes and osteoclasts will be observed. The chondrocyte-specific OPG knockout mice will be constructed to observe the effect of chondrocyte OPG deletion on osteoclast activity and intervertebral disc degeneration. Exploring the mechanism of Jian Yao Mi Gu Pian in delaying intervertebral disc degeneration by regulating the expression of chondrocyte OPG/RANK/RANKL axis, which colud provide a new thinking for the prevention and treatment of intervertebral disc degeneration.