Jikko A, Murakami H, Yan W, Nakashima K, Ohya Y, Satakeda H, Noshiro M, Kawamoto T, Nakamura S, Okada Y, Suzuki F, Kato Y
Department of Biochemistry, School of Dentistry, Hiroshima University, Japan.
Endocrinology. 1996 Jan;137(1):122-8. doi: 10.1210/endo.137.1.8536602.
We examined the effects of cyclic AMP on terminal differentiation and calcification in rabbit growth plate chondrocyte cultures. Dibutyryl cAMP (dbcAMP), as well as 8-bromo-cAMP abolished the increases in chondrocyte size, alkaline phosphatase activity, type X collagen synthesis, 1 alpha, 25-dihydroxyvitamin D3 receptor synthesis, the incorporation of 45Ca into insoluble material, and the calcium content. All of these occurred in parallel untreated cultures during the hypertrophic (terminal) stage. The inhibition of alkaline phosphatase by dbcAMP was detectable after 24 h, and this effect was reversible. dbcAMP and 8-bromo-cyclic AMP inhibited alkaline phosphatase induction and calcification at low concentrations (3-5 microM), whereas 10-30-fold higher concentrations were required to stimulate proteoglycan synthesis. These findings suggest that cAMP plays a crucial role in suppressing terminal differentiation of chondrocyte and cartilage-matrix calcification.
我们研究了环磷酸腺苷（cAMP）对兔生长板软骨细胞培养物中终末分化和钙化的影响。二丁酰环磷腺苷（dbcAMP）以及8-溴环磷腺苷（8-bromo-cAMP）消除了软骨细胞大小增加、碱性磷酸酶活性、X型胶原蛋白合成、1α,25-二羟基维生素D3受体合成、45Ca掺入不溶性物质以及钙含量的增加。在肥大（终末）阶段，所有这些现象在未经处理的平行培养物中都会出现。dbcAMP对碱性磷酸酶的抑制在24小时后即可检测到，且这种作用是可逆的。dbcAMP和8-溴环磷腺苷在低浓度（3-5 microM）时抑制碱性磷酸酶诱导和钙化，而刺激蛋白聚糖合成则需要高10-30倍的浓度。这些发现表明，cAMP在抑制软骨细胞终末分化和软骨基质钙化中起关键作用。
