Li J, Burr D B, Turner C H
Department of Orthopedic Surgery, Indiana University School of Medicine, Indianapolis 46202, USA.
Calcif Tissue Int. 2002 Apr;70(4):320-9. doi: 10.1007/s00223-001-1025-y. Epub 2002 Mar 26.
Prostaglandins mediate adaptive bone formation induced by mechanical loading. Inhibition of cyclooxygenase-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 min) 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-2 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.
前列腺素介导机械负荷诱导的适应性骨形成。用NS - 398抑制环氧化酶 - 2（COX - 2）可有效阻断胫骨内皮质骨表面负荷诱导的成骨作用。在本研究中，我们比较了用NS - 398选择性抑制COX - 2对胫骨内皮质表面和尺骨骨膜表面机械诱导成骨的影响。我们还测试了在机械负荷前（3小时或30分钟）或后（30分钟）不同时间给予NS - 398的效果。机械负荷诱导了胫骨内皮质表面和尺骨骨膜表面的板层骨形成。负荷前3小时口服吲哚美辛或NS - 398可显著降低胫骨内皮质表面和尺骨骨膜表面负荷诱导的骨形成率（BFR）和矿化表面（MS/BS），但不影响矿化沉积率（MAR）。NS - 398使胫骨内皮质表面负荷诱导的MS/BS降低了96%，但在尺骨骨膜表面仅降低了37%（与内皮质表面有显著差异，P <0.05）。吲哚美辛降低MS/BS和BFR的程度小于NS - 398，且对骨膜表面和内皮质表面的影响无差异。这些数据表明，内皮质骨对机械负荷的适应性反应比骨膜骨反应更依赖于COX - 2活性。负荷前3小时腹腔注射NS - 398对胫骨内皮质表面负荷诱导的骨形成率的抑制作用（27%）明显大于负荷前30分钟注射时。当负荷后30分钟给予NS - 398时，骨形成未受到显著抑制。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，而不是与机械诱导的COX - 2表达相关的新前列腺素合成。
