RGD Reference Report - Roles of TNF-alpha, GSK-3beta and RANKL in the occurrence and development of diabetic osteoporosis. - Rat Genome Database

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Roles of TNF-alpha, GSK-3beta and RANKL in the occurrence and development of diabetic osteoporosis.

Authors: Qi, J  Hu, KS  Yang, HL 
Citation: Qi J, etal., Int J Clin Exp Pathol. 2015 Oct 1;8(10):11995-2004. eCollection 2015.
RGD ID: 11555176
Pubmed: (View Article at PubMed) PMID:26722385

OBJECTIVE: To investigate the roles of TNF-alpha, GSK-3beta and RANKL in the occurrence and development of diabetic osteoporosis. METHODS: Diabetic rat model was established; tissue section technology was used to observe the situation of osteoporosis in diabetic rats; rat serum levels of OC, RANKL, GSK-3beta, P38mapk, TNF-alpha and INS were detected by Elisa assay; osteoblasts and osteoclasts were primarily cultured and identified by immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining respectively. The effects of GSK-3beta inhibitors, lithium chloride, TNF-alpha antagonists and RANKL antagonists on the proliferation of osteoblasts and osteoclasts were evaluated; quantitative PCR was used to assess the effects of GSK-3beta inhibitors, lithium chloride, on TNF-alpha and RANKL gene expression in osteoblasts and osteoclasts, and the effects of TNF-alpha and RANKL antagonists on GSK-3beta gene expression in osteoblasts and osteoclasts. RESULTS: Diabetic rat model was successfully established; osteoblasts and osteoclasts were successfully isolated and cultured. Elisa experiments showed that in diabetic model group, the levels of RANKL, GSK-3beta, P38mapk and TNF-alpha were significantly increased, while the levels of osteocalcin (OC) and insulin (INS) were significantly reduced; MTT results showed that osteoclast proliferation in GSK-3beta inhibitor and lithium chloride groups were weaker than the untreated group, while osteoclast proliferation in TNF-alpha antagonist group and RANKL antagonist Group was very close to the untreated group. Osteoblast proliferation in GSK-3beta inhibitor and lithium chloride groups were weaker than the untreated group, while osteoblast proliferation in TNF-alpha antagonist group and RANKL antagonist group was higher than the untreated group. In all of the corresponding groups, cell proliferation in the diabetic group was stronger than the untreated group. In GSK-3beta inhibitor and lithium oxide groups, TNF-alpha and RANKL gene expression levels were elevated, but TNF-alpha and RANKL gene expression levels in the diabetic group were slightly lower than the control group. GSK-3beta gene expression level in TNF-alpha antagonist group and RANKL antagonist group was reduced; GSK-3beta gene expression level in diabetic group was lower than the control group. CONCLUSION: In diabetic rats, TNF-alpha, GSK-3beta and RANKL levels were elevated; GSK-3beta could promote the proliferation of osteoblasts and osteoclasts, and inhibit the expression of TNF-alpha and RANKL; TNF-alpha and RANKL can suppress the proliferation of osteoblasts while had little effect on osteoclast proliferation; they also can promote the GSK-3beta gene expression; interactions between the three broke the balance between osteoblasts and osteoclasts, leading to osteoporosis.



Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Gsk3b  (glycogen synthase kinase 3 beta)


Additional Information