Suppression of prostaglandin synthesis with NS-398 has different effects on endocortical and periosteal bone formation induced by mechanical loading
Suppression of prostaglandin synthesis with NS-398 has different effects on endocortical and periosteal bone formation induced by mechanical loading
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DOI：
10.1007/s00223-001-1025-y
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发表时间：
2002-04-01
影响因子：
4.2
通讯作者：
Turner, CH
中科院分区：
文献类型：
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作者：
Li, J;Burr, DB;Turner, CH
前列腺素介导机械负荷诱导的适应性骨形成。NS-398对环氧合酶-2 （COX-2）的抑制作用可有效阻断胫骨皮质内骨表面负荷诱导的成骨作用。在这项研究中，我们比较了NS-398选择性抑制COX-2对皮质内表面（胫骨）和骨膜表面（尺骨）机械诱导成骨的影响。我们进一步测试了NS-398在机械负荷前（3小时或30分钟）和机械负荷后（30小时）不同时间给药的效果。机械载荷诱导胫骨皮质内表面和尺骨骨膜表面板层骨形成。负荷前3小时口服吲哚美辛或NS-398可显著降低负荷诱导骨形成率（BFR）和矿化表面（MS/BS）。但在胫骨皮质内表面和尺骨骨膜表面的矿物质附着率（MAR）没有变化。NS-398在胫骨皮质内表面使负荷诱导的MS' BS降低96%，而在尺骨骨膜表面仅降低37%（与皮质内表面差异显著，P < 0.05）。吲哚美辛对MS BS和BFR的降低程度低于NS-398，对骨膜和皮质内表面的影响没有差异。这些数据表明，皮质内骨对机械负荷的适应性反应比骨膜骨反应更依赖于cox -活性。与加载前30分钟相比，加载前3小时腹腔注射NS-398可显著抑制加载诱导的胫骨皮质内表面骨形成率（27%）。当NS-398在加载后30分钟给予时，骨形成没有明显抑制。这些数据表明，短暂机械负荷后骨形成的主要细胞机制涉及在施加机械负荷时细胞释放前列腺素，而不是与机械诱导COX-2表达相关的新前列腺素合成。
Prostaglandins mediate adaptive bone formation induced by mechanical loading. Inhibition of evclooxygenase-2 (COX-2) with NS-398 effectively blocks loading-induced osteogenesis on the endocortical bone surface of the tibia. In this study, we compared the effects of selective inhibition of COX-2 with NS-398 on mechanically induced osteogenesis at the endocortical surface (tibia) with that on the periosteal surface (ulna). We further tested the effect of NS-398 administered at different times before (3 hrs or 30 min) or after (30 nun) mechanical loading. Mechanical loading induced lamellar bone formation on the endocortical surface of the tibia and the periosteal surface of the ulna. Oral administration of either indomethacin or NS-398 3 hrs before loading significantly decreased loading-induced bone formation rate (BFR) and mineralizing surface (MS/BS). but not mineral apposition rate (MAR), at the endocortical surface of the tibia and the periosteal surface of the ulna. NS-398 reduced loading-induced MS' BS by 96% on the endocortical surface of the tibia, but only by 37% on the periosteal surface of the ulna (significantly different from endocortical, P < 0.05). Indomethacin reduced MS BS and BFR to a lesser extent than NS-398 and did not have different effects on the periosteal and endocortical surfaces. These data suggest that the endocortical bone adaptive response to mechanical loading is more dependent upon COX-activity than is the periosteal bone response. Intraperitoneal injection of NS-398 3 hrs before loading suppressed load-induced bone formation rate at the endocortical surface of the tibia significantly more (27%) than when administered 30 min before loading. When NS-398 was given 30 min after loading, bone formation was not significantly suppressed. These data suggest that a primary cellular mechanism of bone formation following brief bouts of mechanical loading involves release of prostaglandins from cells at the time mechanical loading is applied, rather than new prostaglandin synthesis associated with a mechanically induced COX-2 expression.