This study focuses on the core pathology of sinew wei （痿）， which is mainly characterized by the fai-lure of qi and blood to nourish the sinews. A mechanical-biological response framework is constructed with mitochondria as a key component， explaining the modern interpretation of the disease location of sinew transmitting to qi and blood pathology. Mechanical loading， as a physical stress stimulus applied to the body， manifests primarily as passive loading formed by external forces such as massage， and active loading resulting from voluntary muscle contractions， such as dao yin （导引）. Mechanical loading can regulate mitochondrial function through two pathways， mechanical signal transduction and metabolic demand-driven regulation. Skeletal muscle mitochondrial dysfunction is regarded as the core microscopic basis of qi imbalance in sinew wei， highlighting the intrinsic connection between qi and mitochondrial energy metabolism， as well as between blood and microcirculatory efficiency. Accordingly， distinct regulatory patterns of mechanical loading are identified. Wei associated with qi stagnation may correspond to mitochondrial network fragmentation and can be treated by regulating qi through passive loading， such as tuina， to restore mitochondrial dynamics. In contrast， wei caused by qi deficiency is attributed to insufficient mitochondrial biogenesis and may be treated by tonifying qi through active loading， such as dao yin， to promote mitochondrial biogenesis. This framework reveals the biological differences in mitochondrial regulation induced by distinct mechanical loading modalities and provides a microscopic mechanism-based explanation for the principle of "treating the same disease with different methods" in sinew wei.

BACKGROUND:Our previous studies have found that polygonatum sibiricum polysaccharide (PSP) promotes osteogenic differentiation of bone marrow mesenchymal stem cel s (BMSCs) by Wnt/β-catenin signaling pathway, but the molecular mechanism is unclear.OBJECTIVE:To investigate the effect of PSP promoting the osteogenic differentiation via Wnt signaling pathways in BMSCs after LRP5 silencing. METHODS:LRP5 interference vectors were constructed and then transfected into C57BL/6 mouse BMSCs cultured in vitro. The transfection efficiency of cel s was calculated under fluorescence inverted microscope and the expression of LRP5 protein was detected by western blot assay. The osteogenic potential of BMSCs after LRP5-siRNA transfection was analyzed by alkaline phosphatase staining, alizarin red staining and western blot assay. Effect of PSP on the osteogenic differentiation of LIRP5-silenced mouse BMSCs was detected by real-time PCR and dual luciferase assay. RESULTS AND CONCLUSION:Compared with the control group, the mineralization ability, the mRNA expressions of Runx2 and Osterix, and the protein expression of LRP5 were significantly decreased in the LRP5-siRNA group (P<0.05). PSP could promote LRP5-siRNA transfected mouse BMSCs differentiating into osteoblasts and significantly upregulated the expressions ofβ-catenin and Osterixin, and also induced the high expression of luciferase reporter gene (TOPFlash) containing wild type TCF binding sites (P<0.05). To conclude, LRP5 plays an important role in the process of mouse BMSCs differentiating into osteoblasts. PSP can promote the osteogenic differentiation of mouse BMSCs by activating the Wnt/β-catenin signaling pathway independent on LRP5.