Abstract：
Platelet-rich plasma (PRP) is a biological blood-derived therapeutic obtained from whole blood that contains higher levels of platelets. PRP has been primarily used to mitigate joint degeneration and chronic pain in osteoarthritis (OA). This clinical applicability is based mechanistically on the release of several proteins by platelets that can restore joint homeostasis. Platelets are the primary source of brain-derived neurotrophic factor (BDNF) outside the central nervous system. Interestingly, BDNF and PRP share key biological activities with clinical applicability for OA management, such as anti-inflammatory, anti-apoptotic, and antioxidant. However, the role of BDNF in PRP therapeutic activities is still unknown. Thus, this work aimed to investigate the implications of BDNF in therapeutic outcomes provided by PRP therapy in vitro and in-vivo, using the MIA-OA animal model in male Wistar rats. Initially, the PRP was characterized, obtaining a leukocyte-poor-platelet-rich plasma (LP-PRP). Our assays indicated that platelets activated by Calcium release BDNF, and suppression of M1 macrophage polarization induced by LP-PRP depends on BDNF full-length receptor, Tropomyosin Kinase-B (TrkB). OA animals were given LP-PRP intra-articular and showed functional recovery in gait, joint pain, inflammation, and tissue damage caused by MIA. Immunohistochemistry for activating transcriptional factor-3 (ATF-3) on L4/L5 dorsal root ganglia showed the LP-PRP decreased the nerve injury induced by MIA. All these LP-PRP therapeutic activities were reversed in the presence of TrkB receptor antagonist. Our results suggest that the therapeutic effects of LP-PRP in alleviating OA symptoms in rats depend on BDNF/TrkB activity.
摘要：
富血小板血浆(PRP)是从含有较高水平血小板的全血获得的生物血液来源的治疗剂。PRP主要用于减轻骨关节炎(OA)中的关节退化和慢性疼痛。这种临床适用性在机械上基于血小板释放几种蛋白质，这些蛋白质可以恢复关节稳态。血小板是中枢神经系统外的脑源性神经营养因子（BDNF）的主要来源。有趣的是,BDNF和PRP共享关键生物活性，临床适用于OA管理，如抗炎，抗凋亡，和抗氧化剂。然而,BDNF在PRP治疗活性中的作用尚不清楚.因此，这项工作旨在研究BDNF在体外和体内PRP治疗提供的治疗结果中的意义，使用雄性Wistar大鼠的MIA-OA动物模型。最初，PRP的特点是，获得富含白细胞的富含血小板的血浆（LP-PRP）。我们的检测表明，钙释放BDNF激活的血小板，LP-PRP诱导的M1巨噬细胞极化的抑制依赖于BDNF全长受体，原肌球蛋白激酶-B(TrkB)。OA动物关节内给予LP-PRP，显示步态功能恢复，关节痛,炎症,MIA引起的组织损伤.L4/L5背根神经节上激活转录因子3（ATF-3）的免疫组织化学显示LP-PRP减轻了MIA引起的神经损伤。所有这些LP-PRP治疗活性在TrkB受体拮抗剂存在下被逆转。我们的结果表明，LP-PRP缓解大鼠OA症状的治疗效果取决于BDNF/TrkB活性。
