Kano J, Sugimoto T, Fukase M, Chihara K
Department of Medicine Kobe University School of Medicine, Japan.
Biochem Biophys Res Commun. 1992 Apr 15;184(1):525-9. doi: 10.1016/0006-291x(92)91226-g.
The present study was performed to characterize the direct involvement of cAMP-dependent protein kinase (PKA) in the regulation of collagen synthesis by parathyroid hormone (PTH) and PTH-related peptide (PTHrP) in osteoblastic osteosarcoma cells, UMR-106. Sp-cAMPS (10(-4)M), a direct activator of PKA, as well as dibutyryl cAMP (dbcAMP, 10(-4)M) significantly inhibited collagen synthesis. Human (h) PTH-(1-34) (10(-7)M) and hPTHrP (10(-7) M) inhibited collagen synthesis to the same degree. Although Rp-cAMPS, which acted directly as an antagonist in the activation of PKA, did not affect collagen synthesis by itself, it significantly antagonized dbcAMP- and Sp-cAMPS-induced inhibition of collagen synthesis. Moreover, Rp-cAMPS antagonized PTH- and PTHrP-induced inhibition of collagen synthesis to the same degree. The present study first indicated that the activation of PKA was directly linked to the regulation of collagen synthesis by PTH in osteoblast and that PTHrP had the same effect on collagen synthesis presumably through the same mechanism as PTH.
本研究旨在确定环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）在成骨细胞性骨肉瘤细胞系UMR-106中直接参与甲状旁腺激素（PTH）和甲状旁腺激素相关肽（PTHrP）对胶原蛋白合成调节的作用。PKA的直接激活剂Sp-cAMPS（10⁻⁴M）以及二丁酰环磷酸腺苷（dbcAMP，10⁻⁴M）均显著抑制胶原蛋白合成。人（h）PTH-（1-34）（10⁻⁷M）和hPTHrP（10⁻⁷M）对胶原蛋白合成的抑制程度相同。尽管直接作为PKA激活拮抗剂的Rp-cAMPS本身不影响胶原蛋白合成，但它能显著拮抗dbcAMP和Sp-cAMPS诱导的胶原蛋白合成抑制。此外，Rp-cAMPS对PTH和PTHrP诱导的胶原蛋白合成抑制具有同等程度的拮抗作用。本研究首次表明，PKA的激活与成骨细胞中PTH对胶原蛋白合成的调节直接相关，并且PTHrP对胶原蛋白合成的影响可能是通过与PTH相同的机制实现的。
