Recombinant myostatin (GDF-8) propeptide enhances the repair and regeneration of both muscle and bone in a model of deep penetrant musculoskeletal injury.
Recombinant myostatin (GDF-8) propeptide enhances the repair and regeneration of both muscle and bone in a model of deep penetrant musculoskeletal injury.
复制标题
DOI：
10.1097/ta.0b013e3181c451f4
复制
发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Liang LF
中科院分区：
文献类型：
--
作者：
Hamrick MW;Arounleut P;Kellum E;Cain M;Immel D;Liang LF
肌生长抑制素（GDF-8）是肌肉生长和发育的有效抑制剂，并且肌生长抑制素也在骨折愈合过程的早期表达。本研究的目的是测试一种新的肌肉生长抑制素抑制剂，重组肌肉生长抑制素前肽，可以提高修复和再生的肌肉和骨骼的情况下，深穿透性损伤的假设。我们使用腓骨截骨术模型，并在小鼠中对外侧间室肌肉（腓骨长肌和腓骨短肌）进行相关损伤，以测试通过全身注射重组肌生长抑制素前肽来阻断活性肌生长抑制素将改善肌肉和骨修复的假设。在经历腓骨截骨术后，将小鼠分配到两个治疗组：接受媒介物（盐水）或重组肌肉生长抑制素前肽（20 mg/kg）的那些。小鼠在手术当天接受一次治疗，手术后5天接受另一次注射，手术后10天接受第三次注射。在截骨手术后15天对小鼠实施安乐死。使用microCT和骨折骨痂的组织学评价评估骨修复。使用损伤部位的Masson三色染色评估肌肉愈合，并使用图像分析来量化纤维化和肌肉再生的程度。在15天内注射三次前肽使体重增加7%，肌肉质量增加近20%（P<0.001）。截骨部位的MicroCT分析显示，截骨后15天，在80%的前肽治疗小鼠中观察到骨痂组织桥接截骨间隙，但在对照（溶剂）治疗小鼠中仅为40%（P<0.01）。MicroCT定量显示，用前肽处理的骨折骨痂的骨体积增加了约30%（P<0.05），并且骨体积的增加伴随着软骨面积的显著增加（P= 0.01）。前肽治疗显著降低了伤口部位的纤维组织分数，并且使肌肉相对于纤维组织的分数增加了20%（P<0.01）。阻断受伤肢体中的肌肉生长抑制素信号传导可改善骨折愈合并增强肌肉再生。这些数据表明，肌生长抑制素抑制剂可能有效改善骨科创伤和肢体损伤的伤口修复。
Myostatin (GDF-8) is known as a potent inhibitor of muscle growth and development, and myostatin is also expressed early in the fracture healing process. The purpose of this study was to test the hypothesis that a new myostatin inhibitor, a recombinant myostatin propeptide, can enhance the repair and regeneration of both muscle and bone in cases of deep penetrant injury. We used a fibula osteotomy model with associated damage to lateral compartment muscles (fibularis longus and brevis) in mice to test the hypothesis that blocking active myostatin with systemic injections of a recombinant myostatin propeptide would improve muscle and bone repair. Mice were assigned to two treatment groups after undergoing a fibula osteotomy: those receiving either vehicle (saline) or recombinant myostatin propeptide (20 mg/kg). Mice received one treatment on the day of surgery, another injection five days following surgery, and a third injection 10 days following surgery. Mice were euthanized 15 days following the osteotomy procedure. Bone repair was assessed using microCT and histological evaluation of the fracture callus. Muscle healing was assessed using Masson trichrome staining of the injury site, and image analysis used to quantify the degree of fibrosis and muscle regeneration. Three propeptide injections over a period of 15 days increased body mass by 7% and increased muscle mass by almost 20% (P<.001). MicroCT analysis of the osteotomy site shows that by 15 days post-osteotomy, bony callus tissue was observed bridging the osteotomy gap in 80% of the propeptide- treated mice, but only 40% of the control (vehicle)-treated mice (P<.01). MicroCT quantification shows that bone volume of the fracture callus was increased by approximately 30% (P<.05) with propeptide treatment, and the increase in bone volume was accompanied by a significant increase in cartilage area (P=.01). Propeptide treatment significantly decreased the fraction of fibrous tissue in the wound site, and increased the fraction of muscle relative to fibrous tissue by 20% (P<.01). Blocking myostatin signaling in the injured limb improves fracture healing and enhances muscle regeneration. These data suggest that myostatin inhibitors may be effective for improving wound repair in cases of orthopaedic trauma and extremity injury.