Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Department of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
PLoS One. 2018 May 31;13(5):e0198088. doi: 10.1371/journal.pone.0198088. eCollection 2018.
Immediately following a fracture, a fibrin laden hematoma is formed to prevent bleeding and infection. Subsequently, the organized removal of fibrin, via the protease plasmin, is essential to permit fracture repair through angiogenesis and ossification. Yet, when plasmin activity is lost, the depletion of fibrin alone is insufficient to fully restore fracture repair, suggesting the existence of additional plasmin targets important for fracture repair. Previously, activated matrix metalloproteinase 9 (MMP-9) was demonstrated to function in fracture repair by promoting angiogenesis. Given that MMP-9 is a defined plasmin target, it was hypothesized that pro-MMP-9, following plasmin activation, promotes fracture repair. This hypothesis was tested in a fixed murine femur fracture model with serial assessment of fracture healing. Contrary to previous findings, a complete loss of MMP-9 failed to affect fracture healing and union through 28 days post injury. Therefore, these results demonstrated that MMP-9 is dispensable for timely fracture union and cartilage transition to bone in fixed femur fractures. Pro-MMP-9 is therefore not a significant target of plasmin in fracture repair and future studies assessing additional plasmin targets associated with angiogenesis are warranted.
骨折发生后，会形成富含纤维蛋白的血肿，以防止出血和感染。随后，通过蛋白酶纤溶酶来有组织地清除纤维蛋白对于通过血管生成和骨化来促进骨折修复至关重要。然而，当纤溶酶活性丧失时，仅仅清除纤维蛋白不足以完全恢复骨折修复，这表明存在其他对骨折修复很重要的纤溶酶靶标。先前已经证明，激活的基质金属蛋白酶 9（MMP-9）通过促进血管生成在骨折修复中发挥作用。鉴于 MMP-9 是纤溶酶的明确靶标，因此假设纤溶酶激活后，前 MMP-9 可促进骨折修复。在固定的小鼠股骨骨折模型中，通过对骨折愈合的连续评估来检验这一假说。与之前的发现相反，MMP-9 的完全缺失并未影响损伤后 28 天内的骨折愈合和连接。因此，这些结果表明 MMP-9 对于固定股骨骨折的及时骨折愈合和软骨向骨的转化是可有可无的。因此，前 MMP-9 不是纤溶酶在骨折修复中的重要靶标，需要进一步研究与血管生成相关的其他纤溶酶靶标。
