Liquiritigenin promotes osteogenic differentiation and prevents bone loss via inducing auto-lysosomal degradation and inhibiting apoptosis.

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 and , 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.