Treatment of Diabetes Osteoporosis by Regulating Autophagy Related PINK1/Parkin Signaling Pathway with the Method of Kidney-Tonifying and Spleen-Invigorating
WEN Xiaochen
LIU Ruoshi
ZHU Ke
LIU Ziying
MA Xiaoyan
GONG Chengjun
XIU Jing
YANG Fang
Abstract：Objective To investigate the therapeutic mechanism of kidney-tonifying and spleen-invigorating therapy on diabetic osteoporosis(DOP)by targeting the PINK1/Parkin pathway-mediated mitochondrial autophagy.Methods Sixty C57BL/6 mice were randomized into seven groups:normal control,DOP model,positive control,kidney-Yin tonification,kidney-Yang tonification,spleen-invigorating,and kidney-tonifying and spleen-invigorating groups.A DOP model was established via a high-fat/high-sucrose diet combined with intraperitoneal streptozotocin(STZ)injections.After 12 weeks of intervention,fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),alkaline phosphatase(ALP),osteocalcin(BGP),tartrate-resistant acid phosphatase(TRAP),calcium(Ca),and phosphorus(P)levels were measured.Femoral histopathology was analyzed by hematoxylin-eosin(HE)staining,bone microstructure parameters were quantified using micro-computed tomography(micro-CT),and protein expression of PINK1,Parkin,LC3-II/I,and p62 was assessed via Western blot.Results Compared to the normal group,the model group exhibited significantly elevated FPG,HbA1c,and TRAP levels(P<0.01),reduced ALP and BGP(P<0.01),and decreased trabecular bone mineral density(BMD)and bone volume fraction(BV/TV)(P<0.05).All treatment groups showed improved glycemic control(HbA1c reduction,P<0.01),ameliorated bone histopathology,and restored bone microstructure compared to the model group.Compared with the model group,all treatment groups showed significant reductions in HbA1c levels(P<0.01)and improvements in bone histopathological damage and microstructure.In the kidney-tonifying and spleen-invigorating group,ALP and BGP levels were elevated(P<0.01),while TRAP levels decreased(P<0.01),indicating its potential role in ameliorating bone metabolism.Furthermore,the kidney-tonifying and spleen-invigorating group exhibited increased expression levels of PINK1,Parkin,and LC3-II/I(P<0.05),along with reduced p62 protein expression(P<0.01),suggesting activation of mitochondrial autophagy(mitophagy).Conclusion The kidney-tonifying and spleen-invigorating method improves DOP-induced bone metabolic disorders and microstructural damage by enhancing mitophagy through activation of the PINK1/Parkin signaling pathway.
Keywords：Diabetic osteoporosisKidney-tonifying and spleen-invigorating therapyPINK1/Parkin signaling pathwayMitophagy
Publication Date：2025-04-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 649-654 )