Malange Kaue Franco, de Souza Douglas Menezes, Lemes Julia Borges Paes, Fagundes Cecilia Costa, Oliveira Anna Lethicia Lima, Pagliusi Marco Oreste, Carvalho Nathalia Santos, Nishijima Catarine Massucato, da Silva Cintia Rizoli Ruiz, Consonni Silvio Roberto, Sartori Cesar Renato, Tambeli Claudia Herrera, Parada Carlos Amilcar
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Rua Carl Von Linnaeus, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-864, Brazil.
Department of Pharmacology, School of Medical Sciences, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
Inflammation. 2025 Feb;48(1):426-446. doi: 10.1007/s10753-024-02072-9. Epub 2024 Jun 21.
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.
富血小板血浆（PRP）是一种从全血中获得的生物血液衍生疗法，其血小板水平较高。PRP主要用于减轻骨关节炎（OA）中的关节退变和慢性疼痛。这种临床适用性在机制上基于血小板释放的几种蛋白质，这些蛋白质可以恢复关节内环境稳定。血小板是中枢神经系统外脑源性神经营养因子（BDNF）的主要来源。有趣的是，BDNF和PRP在OA管理的临床适用性方面具有关键的生物学活性，如抗炎、抗凋亡和抗氧化。然而，BDNF在PRP治疗活性中的作用仍然未知。因此，本研究旨在使用雄性Wistar大鼠的MIA - OA动物模型，在体外和体内研究BDNF对PRP治疗效果的影响。最初，对PRP进行了表征，获得了低白细胞富血小板血浆（LP - PRP）。我们的检测表明，钙释放激活的血小板释放BDNF，并且LP - PRP诱导的M1巨噬细胞极化抑制依赖于BDNF全长受体原肌球蛋白激酶 - B（TrkB）。给OA动物关节内注射LP - PRP后，其步态、关节疼痛、炎症和MIA引起的组织损伤均有功能恢复。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诱导的神经损伤。在存在TrkB受体拮抗剂的情况下，所有这些LP - PRP的治疗活性均被逆转。我们的结果表明，LP - PRP在减轻大鼠OA症状方面的治疗效果取决于BDNF/TrkB活性。
