Shen V, Kohler G, Jeffrey J J, Peck W A
Department of Bone and Mineral Metabolism, Jewish Hospital at Washington University Medical Center, St. Louis, MO.
J Bone Miner Res. 1988 Dec;3(6):657-66. doi: 10.1002/jbmr.5650030611.
Parathyroid hormone, prostaglandin E2, 1 alpha,25-dihydroxyvitamin D3, interleukin-1, tumor necrosis factor alpha, and epidermal growth factor, all known stimulators of bone resorption, markedly enhanced collagenase secretion by rat fetus osteoblastlike cells in primary culture as judged by enzyme-linked immunosorbent assay. Untreated cells contained no immunostainable or extractable collagenase. Collagenase was detected in the treated cells and media only after 1-3 h of treatment, and there was no increment in collagenase activity when cells were treated in the presence of actinomycin D or cycloheximide. Cells secreted collagenase in a latent form and also elaborated collagenase inhibitor; chromatographic separation of collagenase from collagenase inhibitor and subsequent activation of the collagenase with trypsin yielded the active species in stimulated but not in unstimulated cells. The ability of individual prostanoids, among seven tested, to promote collagenase production correlated positively with their reported capacity to promote bone resorption. Interferon-gamma (IFN-gamma), a known resorption inhibitor, blocked the increment in collagenase production caused by all agents tested. These results indicate a close linkage between stimulation of bone resorption and collagenase production by osteoblastlike cells. Various resorption stimulators, including some not previously tested for effects on collagenase, augment the de novo synthesis and secretion of collagenase and act by an IFN-gamma-inhibitable mechanism.
甲状旁腺激素、前列腺素E2、1α,25 - 二羟维生素D3、白细胞介素 - 1、肿瘤坏死因子α和表皮生长因子，所有这些已知的骨吸收刺激剂，通过酶联免疫吸附测定法判断，均能显著增强原代培养的大鼠胎儿成骨样细胞的胶原酶分泌。未处理的细胞不含可免疫染色或可提取的胶原酶。仅在处理1 - 3小时后，在处理过的细胞和培养基中才检测到胶原酶，并且当细胞在放线菌素D或环己酰亚胺存在下处理时，胶原酶活性没有增加。细胞以潜伏形式分泌胶原酶，并且还产生胶原酶抑制剂；用胰蛋白酶从胶原酶抑制剂中色谱分离胶原酶并随后激活胶原酶，在受刺激的细胞中产生了活性形式，但在未受刺激的细胞中未产生。在七种测试的前列腺素中，单个前列腺素促进胶原酶产生的能力与其促进骨吸收的报道能力呈正相关。干扰素 - γ（IFN - γ），一种已知的吸收抑制剂，阻断了所有测试试剂引起的胶原酶产生的增加。这些结果表明骨吸收刺激与成骨样细胞胶原酶产生之间存在密切联系。各种吸收刺激剂，包括一些以前未测试过对胶原酶影响的试剂，增加了胶原酶的从头合成和分泌，并通过IFN - γ可抑制的机制起作用。
