Research progress in the effects of high glucose on signaling pathways in bone metabolism / 中华骨科杂志

ABSTRACT

Diabetes mellitus (DM),a highly prevalent chronic metabolic disorder,can damage multiple organ systens.For instance,in the skeletal system,DM can lead to osteoporosis,delayed fracture healing or nonunion of fractures,which not only affects the prognosis of bone diseases and quality of life but also leads to huge medical and economic burden.The main reason of these skeletal complications is the disruption of the balance between bone formation and bone resorption,which leads to the disorders of bone metabolism.The mechanism of bone metabolism disorders in DM patients is determined by many biological factors,including high glucose (HG),oxidative stress,accumulation of advanced glycation end products (AGEs),insulin levels,inflammatory factors,growth factors,adipocytokines and hypaglycemic agents.Furthermore,as an important feature of DM,HG has obvious effects on bone metabolism mainly by acting on signal transduction pathways,including PI3K/Akt pathway,cAMP/PKA pathway,wnt pathway,MARK pathway,AMPK/mTOR/ULK1 pathway,BMP pathway,EphrinB2/EphB4 pathway,PPARγ pathway and NF-κB pathway.The above mentioned signal pathways regulate the proliferation,differentiation,apoptosis and aging of cells,such as bone marrow mesenchymal stem cells (BMSCs),osteoblasts and osteoclasts.These research areas have become the current hotspot for investigation.Although some studies has been conducted in these research areas,several limitations are still exist especially in vivo study.Thus,further studies are required.The present article reviews the effects of HG on bone metabolism signaling pathways.The purpose of this review is conducive to further understand the molecular mechanism of bone metabolism regulated by HG,and to provide theoretical basis and orientations for prevention and treatment of diabetic bone diseases.