MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, United States of America.
Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, United States of America.
PLoS One. 2021 Sep 16;16(9):e0251166. doi: 10.1371/journal.pone.0251166. eCollection 2021.
Platelet-rich plasma (PRP) is a widely used autologous treatment for tendon injuries in clinics. Platelets (PLTs) are a major source of high mobility group box1 (HMGB1) that is gaining attention as a chemoattractant that can recruit stem cells to the wound area to enhance healing of injured tissues; however, the contribution of PLT HMGB1 in wounded tendon healing remains unexplored. This study investigated the effect of PLT HMGB1 within PRP on tendon healing using PLT HMGB1 knockout (KO) and GFP mice. A window defect was created in the patellar tendons of both groups of mice, and wounds were treated with either saline, PRP isolated from PLT HMGB1-KO mice, or PRP isolated from GFP mice. Seven days post-treatment, animals were sacrificed and analyzed by gross inspection, histology, and immunostaining for characteristic signs of tendon healing and repair. Our results showed that in comparison to mice treated with PRP from PLT HMGB1-KO mice, wounds treated with PRP from GFP mice healed faster and exhibited a better organization in tendon structure. Mice treated with PRP from PLT HMGB1-KO mice produced tendon tissue with large premature wound areas and low cell densities. However, wounds of PLT HMGB1-KO mice showed better healing with PRP from HMGB1-KO mice compared to saline treatment. Moreover, wounds treated with PRP from GFP mice had increased extracellular HMGB1, decreased CD68, increased stem cell markers CD146 and CD73, and increased collagen III protein expression levels compared to those treated with PRP from PLT HMGB1-KO mice. Thus, PLT HMGB1 within PRP plays an important role in tendon wound healing by decreasing inflammation, increasing local HMGB1 levels, and recruiting stem cells to the wound area in the tendon. Our findings also suggest that the efficacy of PRP treatment for tendon injuries in clinics may depend on PLT HMGB1 within PRP preparations.
富含血小板的血浆（PRP）是临床上广泛应用于治疗肌腱损伤的自体治疗方法。血小板（PLT）是高迁移率族蛋白 1（HMGB1）的主要来源，作为趋化因子，HMGB1 可以招募干细胞到伤口部位，增强受伤组织的愈合，这一点越来越受到关注；然而，PLT HMGB1 在受伤肌腱愈合中的作用仍未得到探索。本研究使用 PLT HMGB1 敲除（KO）和 GFP 小鼠，研究了 PRP 中 PLT HMGB1 对肌腱愈合的影响。在两组小鼠的髌腱上创建一个窗口缺陷，并用盐水、来自 PLT HMGB1-KO 小鼠的 PRP 或来自 GFP 小鼠的 PRP 处理伤口。治疗后 7 天，处死动物，通过大体检查、组织学和免疫染色分析特征性的肌腱愈合和修复迹象。我们的结果表明，与用来自 PLT HMGB1-KO 小鼠的 PRP 治疗的小鼠相比，用来自 GFP 小鼠的 PRP 治疗的伤口愈合更快，并且肌腱结构更有组织。用来自 PLT HMGB1-KO 小鼠的 PRP 治疗的小鼠产生的肌腱组织具有较大的过早伤口区域和较低的细胞密度。然而，与盐水治疗相比，用来自 HMGB1-KO 小鼠的 PLT HMGB1-KO 小鼠的 PRP 治疗的 PLT HMGB1-KO 小鼠的伤口愈合更好。此外，与用来自 PLT HMGB1-KO 小鼠的 PRP 治疗的伤口相比，用来自 GFP 小鼠的 PRP 治疗的伤口具有更高的细胞外 HMGB1、更少的 CD68、更多的干细胞标志物 CD146 和 CD73，以及更高的胶原蛋白 III 蛋白表达水平。因此，PRP 中的 PLT HMGB1 通过减少炎症、增加局部 HMGB1 水平以及招募干细胞到肌腱中的伤口部位，在肌腱伤口愈合中发挥重要作用。我们的研究结果还表明，PRP 治疗肌腱损伤的临床疗效可能取决于 PRP 制剂中的 PLT HMGB1。
