Monosodium urate monohydrate crystals inhibit osteoblast viability and function: implications for development of bone erosion in gout

成骨细胞 活力测定 破骨细胞 运行x2 骨钙素 痛风 鱼腥草素骨 医学 骨细胞 内科学 内分泌学 细胞生物学 化学 碱性磷酸酶 生物化学 细胞 生物 体外 受体
作者
Ashika Chhana,Karen E. Callon,Bregina Pool,Dorit Naot,Maureen Watson,Greg Gamble,Fiona McQueen,Jillian Cornish,Nicola Dalbeth
出处
期刊:Annals of the Rheumatic Diseases [BMJ]
卷期号:70 (9): 1684-1691 被引量:72
标识
DOI:10.1136/ard.2010.144774
摘要

Bone erosion is a common manifestation of chronic tophaceous gout.To investigate the effects of monosodium urate monohydrate (MSU) crystals on osteoblast viability and function.The MTT assay and flow cytometry were used to assess osteoblast cell viability in the MC3T3-E1 and ST2 osteoblast-like cell lines, and primary rat and primary human osteoblasts cultured with MSU crystals. Quantitative real-time PCR and von Kossa stained mineralised bone formation assays were used to assess the effects of MSU crystals on osteoblast differentiation using MC3T3-E1 cells. The numbers of osteoblasts and bone lining cells were quantified in bone samples from patients with gout.MSU crystals rapidly reduced viability in all cell types in a dose-dependent manner. The inhibitory effect on cell viability was independent of crystal phagocytosis and was not influenced by differing crystal length or addition of serum. Long-term culture of MC3T3-E1 cells with MSU crystals showed a reduction in mineralisation and decreased mRNA expression of genes related to osteoblast differentiation such as Runx2, Sp7 (osterix), Ibsp (bone sialoprotein), and Bglap (osteocalcin). Fewer osteoblast and lining cells were present on bone directly adjacent to gouty tophus than bone unaffected by tophus in patients with gout.MSU crystals have profound inhibitory effects on osteoblast viability and differentiation. These data suggest that bone erosion in gout occurs at the tophus-bone interface through alteration of physiological bone turnover, with both excessive osteoclast formation, and reduced osteoblast differentiation from mesenchymal stem cells.
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