Targeting MDK alleviates bone loss via dual regulation of osteogenic differentiation and inflammatory cytokine expressionOA
Growth factors are bioactive molecules that play crucial roles in regulating growth,development,and disease processes,both locally and systemically,Identifying growth factors involved in bone homeostasis and targeting them is a key strategy for treating bone metabolic diseases,In this study,we observed significantly elevated serum levels of midkine(MDK)in patients with postmenopausal osteoporosis and in ovariectomized mice,based on clinical data and animal experiments,We also identified a negative correlation between MDK levels and bone mineral density,The small molecule inhibitor of MDK,iMDK,effectively mitigated estrogen deficiency-induced bone loss by promoting bone formation and inhibiting inflammatory factors,Our in vitro experiments further revealed that recombinant MDK protein dose-dependently inhibited osteogenic differentiation,Transcriptome analysis showed that recombinant MDK protein affected osteogenic differentiation through the PI3K/AKT signaling pathway,Additionally,it increased the expression of inflammatory cytokines,including IL-6,TNF-α,and IL-1β,via the NF-κB signaling pathway,These findings suggest that MDK could serve as a novel therapeutic target for postmenopausal osteoporosis,and that iMDK may be a promising therapeutic candidate.
Xieyidai Ruze;Yutong Hu;Xiongyi Wang;Houfu Lai;Ruizhi Zhang;Sheng Pan;Jiajun Zhang;Yike Wang;Simin Yun;Ying Xu;Junjie Li;Youjia Xu
Department of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,ChinaDepartment of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,ChinaDepartment of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,ChinaDepartment of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,ChinaDepartment of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,ChinaDepartment of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,ChinaDepartment of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,ChinaDepartment of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,ChinaDepartment of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,ChinaJiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Su Genomic Resource Center,Medical College of Soochow University,Suzhou,Jiangsu 215000,ChinaDepartment of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,China The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine),Hangzhou,Zhejiang 310006,ChinaDepartment of Orthopedics,Department of Osteoporosis,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215004,China
医药卫生
Growth factorsInflammatorycytokinesMDKOsteoblastTargeted therapy
《Genes & Diseases》 2026 (3)
P.393-408,16
supported by the Natural Science Foundation of China(No.82372455)Jiangsu Provincial Medical Key Laboratory Cultivation Unit(China)(No.JSDW202254)Special Project of"Technological Innovation"Project of CNNC Medical Industry Co.,Ltd.,China(No.ZHYLZD2023001)Zhejiang Provincial Natural Science Foundation of China(No.LBZ24H060001).
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