The COX-2 pathway is essential during early stages of skeletal muscle regeneration
The COX-2 pathway is essential during early stages of skeletal muscle regeneration
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DOI：
10.1152/ajpcell.00088.2004
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发表时间：
2004-08-01
影响因子：
5.5
通讯作者：
Pavlath, GK
中科院分区：
文献类型：
--
作者：
Bondesen, BA;Mills, ST;Pavlath, GK
骨骼肌再生包括几个重叠的细胞过程，包括炎症和肌生成。前列腺素（PGs）可以调节肌肉再生，因为它们调节炎症并参与体外肌发生的各个阶段。PG的合成由不同的环氧合酶（考克斯）异构体催化，而这些异构体可被非甾体类药物抑制。虽然采用非甾体抗炎药的实验表明PG参与组织修复，但PG如何调节肌肉再生仍不清楚，不同考克斯亚型的潜在不同作用尚未研究。为了解决这些问题，在损伤前开始用考克斯-1-或考克斯-2-选择性抑制剂（分别为SC-560和SC-236）长期治疗的小鼠胫骨前肌中诱导局部冷冻损伤。在损伤后5周的时间点分析再生肌纤维的大小，发现SC-236和考克斯-2（-/-）肌肉中再生肌纤维的大小减少，但不受SC-560的影响。相比之下，SC-236在损伤后7天开始给药时对肌纤维生长没有影响。SC-236治疗和考克斯-2（-/-）肌肉中肌纤维生长的衰减与损伤后早期成肌细胞和肌内炎性细胞数量的减少有关。总之，这些数据表明，考克斯-2依赖性PG合成是在肌肉再生的早期阶段所必需的，因此提高了在肌肉损伤或疾病患者中使用考克斯-2选择性抑制剂的谨慎性。
Skeletal muscle regeneration comprises several overlapping cellular processes, including inflammation and myogenesis. Prostaglandins (PGs) may regulate muscle regeneration, because they modulate inflammation and are involved in various stages of myogenesis in vitro. PG synthesis is catalyzed by different isoforms of cyclooxygenase (COX), which are inhibited by nonsteroidal antiinflammatory drugs. Although experiments employing nonsteroidal anti-inflammatory drugs have implicated PGs in tissue repair, how PGs regulate muscle regeneration remains unclear, and the potentially distinct roles of different COX isoforms have not been investigated. To address these questions, a localized freeze injury was induced in the tibialis anterior muscles of mice chronically treated with either a COX-1- or COX-2-selective inhibitor (SC-560 and SC-236, respectively), starting before injury. The size of regenerating myofibers was analyzed at time points up to 5 wk after injury and found to be decreased by SC-236 and in COX-2(-/-) muscles, but unaffected by SC-560. In contrast, SC-236 had no effect on myofiber growth when administered starting 7 days after injury. The attenuation of myofiber growth by SC-236 treatment and in COX-2(-/-) muscles is associated with decreases in the number of myoblasts and intramuscular inflammatory cells at early times after injury. Together, these data suggest that COX-2-dependent PG synthesis is required during early stages of muscle regeneration and thus raise caution about the use of COX-2-selective inhibitors in patients with muscle injury or disease.