Mechanism of Wenshen Tongluo Decoction on diabetic nephropathy-induced osteoporosis in rats
XU Ying-kai
JIANG Jian-feng
WANG Lei
Abstract：Objective To investigate the effects and potential mechanisms of Wenshen Tongluo Formula in rats with diabetic nephropathy-induced osteoporosis(DNOP).Methods Male Sprague-Dawley(SD)rats,aged 9 weeks,were induced with DNOP using streptozotocin(STZ).The rats were divided into the following groups:Control Group(n=10),DNOP Group(n=10),Low-dose Wenshen Tongluo Formula Group(n=10),Medium-dose Wen-shen Tongluo Formula Group(n=10),High-dose Wenshen Tongluo Formula Group(n=10),and Alendronate(ALN)Group(positive control,n=10).Enzyme-linked immunosorbent assay(ELISA)kits were used to detect tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),interleukin-8(IL-8),interleukin-1β(IL-1β),al-kaline phosphatase(ALP),and tartrate-resistant acid phosphatase(TRAP)levels.Western blotting was used to ana-lyze the expression of proteins related to the Wnt/YAP/TAZ signaling pathway,epithelial-mesenchymal transition(EMT)markers,and osteoblast differentiation proteins.Results Treatment with Wenshen Tongluo Formula significantly improved the overall health,kidney function,and pathological changes in the kidneys of DNOP rats.Wenshen Tongluo Formula reduced the levels of TNF-α,IL-6,IL-8,IL-1β,ALP,and TRAP,increased serum calcium and phos-phorus levels,and decreased urinary calcium and phosphorus levels.Additionally,the formula significantly improved bone mineral density(BMD),bone volume(BV),and bone microstructure in DNOP rats.The elastic modulus,ultimate load,and bending strength of the femur were also significantly enhanced.After treatment,the expression of α-SMA,vi-mentin,Wnt Family Member 3A(Wnt3a),phosphorylated Yes-associated protein(p-YAP),and TAZ was signifi-cantly downregulated,while the expression of E-cadherin,Bone Morphogenetic Protein 4(BMP-4),Bone Morphoge-netic Protein 7(BMP-7),Runt-related transcription factor 2(Runx2),osteocalcin,and collagen type Ⅰ alpha 1 chain(Col1a1)was significantly upregulated.Conclusion This study suggests that Wenshen Tongluo Formula has thera-peutic effects on DNOP,which may be achieved through the downregulation of the Wnt/YAP/TAZ signaling pathway.
Keywords：Wnt/YAP/TAZ pathwayWenshen Tongluo Formuladiabetic nephropathydiabetic osteoporosis
Publication Date：2025-05-15
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：9( 672-680 )