Osteoporosis (OP) is a debilitating skeletal abnormality involving bone remodeling and bone cell homeostasis characterized by decreased bone strength and high fracture risk. A novel therapeutic intervention for OP by manipulating cellular autophagy–apoptosis processes to promote skeletal homeostasis is presented. Protective effects of the naturally occurring plant extract Liquiritigenin (LG) were demonstrated in an ovariectomy (OVX)-OP mouse model and preosteoblast MC3T3-E1 cells. Micro-CT and histological staining assessments of skeletal phenotype were applied alongside detection of autophagy activity in osteocytes and MC3T3-E1 cells by transmission electron microscopy (TEM). The effects of LG on chloroquine (CQ)- and the apoptosis-inducing TS-treated osteogenic differentiations and status of lysosomes within MC3T3-E1 cells were analyzed by Neutral red, Alizarin red S and alkaline phosphatase (ALP) staining and Western blot assays. Treatment with LG prevented bone loss, increased osteogenic differentiation in vivo and in vitro, and inhibited osteoclast formation to some extent. TEM analyses revealed that LG can improve auto-lysosomal degradation within osteocytes from OVX mice and MC3T3-E1 cells. The abnormal status of lysosomes associated with CQ and TS treatments was notably alleviated by LG which also reduced levels of apoptosis-induced inhibition of osteogenic differentiation and averted abnormal osteogenic differentiation as a consequence of a blockage in autolysosome degradation. Overall, LG stimulates bone growth in OVX mice through increased osteogenic differentiation and regulation of autophagy-apoptosis mechanisms, presenting an auspicious natural therapy for OP.

骨质疏松症 (OP) 是一种使人衰弱的骨骼异常，涉及骨重塑和骨细胞稳态，其特征是骨强度下降和骨折风险高。提出了一种通过操纵细胞自噬-凋亡过程促进骨骼稳态的新型 OP 治疗干预措施。天然存在的植物提取物甘草素 (LG) 的保护作用在卵巢切除术 (OVX)-OP 小鼠模型和前成骨细胞 MC3T3-E1 细胞中得到证实。骨骼表型的显微 CT 和组织学染色评估与通过透射电子显微镜 (TEM) 检测骨细胞和 MC3T3-E1 细胞中的自噬活性一起应用。通过中性红、茜素红 S 和碱性磷酸酶 (ALP) 染色和蛋白质印迹分析，分析了 LG 对氯喹 (CQ) 和细胞凋亡诱导 TS 处理的成骨分化和 MC3T3-E1 细胞内溶酶体状态的影响。用 LG 治疗可防止骨质流失，增加成骨分化体内外均有一定的抑制破骨细胞形成的作用。TEM 分析表明，LG 可以改善 OVX 小鼠和 MC3T3-E1 细胞骨细胞内的自身溶酶体降解。LG 显着缓解了与 CQ 和 TS 处理相关的溶酶体异常状态，LG 还降低了细胞凋亡诱导的成骨分化抑制水平，并避免了由于自溶酶体降解受阻而导致的异常成骨分化。总的来说，LG 通过增加成骨分化和调节自噬-凋亡机制来刺激 OVX 小鼠的骨骼生长，为 OP 提供了一种有利的自然疗法。