Diabetes osteoporosis is a chronic complication of diabetes mellitus(DM)and is associated with osteoclast for-mation and enhanced bone resorption.Specnuezhenide(SPN)is an active compound with anti-inflammatory and immunomodulatory properties.However,the roles of SPN in diabetic osteoporosis remain unknown.In this study,primary bone marrow macrophages(BMMs)were pretreated with SPN and were stimulated with receptor activator of nuclear factor kappa B ligand(RANKL;50 ng/mL)to induce osteoclastogenesis.The number of osteoclasts was detected by tartrate-resistant acid phosphatase(TRAP)staining.The protein levels of cellular oncogene fos/nuclear factor of activated T cells c1(c-Fos/NFATc1),nuclear factor kappa-B(NF-κB),and mitogen-activated protein kinases(MAPKs)were evaluated by western blot analysis.NF-κB luciferase assays were used to examine the role of SPN in NF-κB activation.The DM model group received a high-glucose,high-fat diet and was then intraperitoneally injected with streptozotocin(STZ).Micro-CT scanning,serum biochemical analysis,histological analysis were used to assess bone loss.We found that SPN suppressed RANKL-induced osteoclast formation and that SPN inhibited the expression of osteoclast-related genes and c-Fos/NFATc1.SPN inhibited RANKL-induced activation of NF-κB and MAPKs.In vivo experiments revealed that SPN suppressed diabetes-induced bone loss and the number of osteo-clasts.Furthermore,SPN decreased the levels of bone turnover markers and increased the levels of runt-related transcription factor 2(RUNX2),osteoprotegerin(OPG),calcium(Ca)and phosphorus(P).SPN also regulated dia-betes-related markers.This study suggests that SPN suppresses diabetes-induced bone loss by inhibiting RANKL-induced osteoclastogenesis,and provides an experimental basis for the treatment of diabetic osteoporosis.

Xiaoshuang Ye;Juanjuan Jiang;Juan Yang;Wenyan Yan;Luyue Jiang;Yan Chen

Department of Nephrology,the Affiliated Geriatric Hospital of Nanjing Medical University,Nanjing 210024,China

生物化学与生物物理学报（英文版）

[1]Xiaoshuang Ye;Juanjuan Jiang;Juan Yang;Wenyan Yan;Luyue Jiang;Yan Chen-.Specnuezhenide suppresses diabetes-induced bone loss by inhibiting RANKL-induced osteoclastogenesis)[J].生物化学与生物物理学报（英文版）,2022(08):1080-1089

Specnuezhenide

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