关键词: knee macrophage muscle restoration osteoarthritis pain quadriceps satellite cell

来  源:   DOI:10.1093/rb/rbae077   PDF(Pubmed)

Abstract:
Quadriceps muscles play a pivotal role in knee osteoarthritis (OA) progression and symptom manifestation, particularly pain. This research investigates the therapeutic effectiveness of muscle enhancement and support therapy (MEST), a recently developed device intended for intramuscular insertion of cog polydioxanone filaments, in quadriceps restoration to alleviate OA pain. Knee OA was induced in Sprague Dawley rats via monoiodoacetate injections. MEST or sham treatment was performed in OA or Naive rat quadriceps. Pain was assessed using paw withdrawal threshold and weight bearing. Quadriceps injury and recovery via MEST were evaluated using biomarkers, tissue morphology, muscle mass, contractile force and hindlimb torque. Satellite cell and macrophage activation, along with their activators, were also assessed. Data were compared at 1- and 3-weeks post-MEST treatment (M-W1 and M-W3). MEST treatment in OA rats caused muscle injury, indicated by elevated serum aspartate transferase and creatinine kinase levels, and local β-actin changes at M-W1. This injury triggered pro-inflammatory macrophage and satellite cell activation, accompanied by heightened interleukin-6 and insulin-like growth factor-1 levels. However, by M-W3, these processes gradually shifted toward inflammation resolution and muscle restoration. This was seen in anti-inflammatory macrophage phenotypes, sustained satellite cell activation and injury markers regressing to baseline. Quadriceps recovery in mass and strength from atrophy correlated with substantial OA pain reduction at M-W3. This study suggests that MEST-induced minor muscle injury triggers macrophage and satellite cell activation, leading to recovery of atrophied quadriceps and pain relief in OA rats.
摘要:
股四头肌在膝骨关节炎(OA)的进展和症状表现中起着关键作用,特别是疼痛。这项研究调查了肌肉增强和支持疗法(MEST)的治疗效果,一种最近开发的用于肌内插入cog聚二恶烷酮细丝的装置,在股四头肌修复中缓解OA疼痛。通过单碘乙酸盐注射在SpragueDawley大鼠中诱导膝关节OA。在OA或幼稚大鼠股四头肌中进行MEST或假治疗。使用爪退缩阈值和负重来评估疼痛。使用生物标志物评估股四头肌损伤和通过MEST恢复,组织形态学,肌肉质量,收缩力和后肢扭矩。卫星细胞和巨噬细胞活化,以及他们的活化剂,也进行了评估。在MEST治疗后1周和3周比较数据(M-W1和M-W3)。MEST治疗OA大鼠引起的肌肉损伤,血清天冬氨酸转移酶和肌酐激酶水平升高,和M-W1处的局部β-肌动蛋白变化。这种损伤引发了促炎巨噬细胞和卫星细胞活化,伴随着白细胞介素-6和胰岛素样生长因子-1水平升高。然而,通过M-W3,这些过程逐渐转向炎症消退和肌肉恢复。这在抗炎巨噬细胞表型中可见,持续的卫星细胞活化和损伤标志物回归基线。在M-W3时,股四头肌从萎缩中恢复的质量和力量与显著减轻OA疼痛相关。这项研究表明,MEST诱导的轻微肌肉损伤会触发巨噬细胞和卫星细胞激活,导致OA大鼠股四头肌萎缩恢复和疼痛缓解。
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