Advanced glycation end products affect growth and function of osteoblasts

作者：Franke S^*; Ruester C; Pester J; Hofmann G; Oelzner P; Wolf G

来源：Clinical and Experimental Rheumatology, 2011, 29(4): 650-660.

• Osteoblasts
• Advanced Glycation End Products
• RAGE (receptor for advanced glycation end products)
• NF kappa B
• bone formation and resorption

Objective
Advanced glycation end products (AGEs) have been implicated in the pathogenesis of bone-destructive disorders. Yet reports on the influence of AGEs on human osteoblasts remain lacking. The aim of the study is to investigate the influence of AGE-modified bovine serum albumin (AGE-BSA)On cell growth and expression of osteoblastic markers associated with osteogenesis and osteoclastogenesis.
Methods
Human osteoblasts established from bone tissue specimens were stimulated with AGE-BSA and investigated in vitro. Expression of mRNA for the receptor for AGEs (RAGE), nuclear factor kappa B subunit p65 (NF kappa B p65), tumour necrosis factor alpha (TNF-alpha), matrix metallo proteinase-1 (MMP-1), receptor activator of NF kappa B ligand (RANKL), osteoprotegerin, collagen type 1 (Coll), osteocalcin (OC) and alkaline phosphatase (ALP) were measured using real-time polymerase chain reaction (PCR). Respective protein expressions were evaluated by western blot analysis or ELISA. NF kappa B activation was investigated by luciferase assay and electrophoretic mobility shift assay (EMSA). Cell cycle analysis, cell proliferation and markers of necrosis and early apoptosis were assessed.
Results
AGE-BSA was actively taken up into osteoblasts and induced cell cycle arrest and an increase in necrotic, but not apoptotic cells. The increased expression of RAGE and TNF-alpha together with NF kappa B activation indicates an AGE-mediated inflammatory response. The decreased expression of Coil, OC and ALP presumably reflects a diminished osteogenic potential, whereas upregulation of RANKL and TNF-alpha enhances osteoclastogenesis.
Conclusion
The present study demonstrates that AGE-BSA affects the growth and Junction of osteoblasts. Modulation of the expression of various target genes involved in bone metabolism provides evidence that AGEs accumulated in the bone matrix have the potential to suppress osteogenic and to promote osteoclastogenic properties of osteoblasts in vivo, thereby leading to functional and structural impairment of bone.

• 出版日期2011-8