Brain-derived neurotrophic factor (BDNF) as an important protein for therapeutic effects of platelet-rich plasma in an experimental osteoarthritis model

Author(s)

Kauê Franco Malange

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2021-12-06

Examining board members

Carlos Amílcar Parada; Carolina Caliari Oliveira; Luiz Fernando Ferrari; Maria Cláudia Gonçalves de Oliveira; Marucia Chacur

• Advisor: Carlos Amílcar Parada

Abstract

Platelet rich plama (PRP) represents one of the promising therapies for joint repair and control of chronic pain in osteoarthritis (OA). By releasing several proteins when activated in the injured site, platelets affect tissue repair regulating the inflammatory process, and triggering tissue anabolism and healing. Thus, in relation to arthroplasty surgeries, PRP therapy has been shown to be more effective for providing a gradual resumption of joint homeostasis, preserving the natural aspect of joint compartment, and enabling the control of chronic pain, which in many cases does not resolve after surgical interventions. Outside the central nervous system, platelets represent the major source of brain-derived neurotrophic factor (BDNF), with concentrations ranging from 100 to 1000 more in relation to neuronal cells that synthesize this growth factor. Among the therapeutic activities performed by BDNF and its receptor (Trk-B) with potential application in the pathophysiology of osteoarthritis, its anti-inflammatory, anti-apoptotic and antioxidant actions stand out. Studies show that there is a release of BDNF by synovial cells from osteoarthritic joints and that this protein is also found in high concentration in synovial fluid, having a direct relationship with the clinical prognosis of patients. Thus, considering platelets as an important therapeutic source of BDNF and the possible relationship of this neurotrophic factor with joint repair, the aim of this study was to evaluate the contribution of BDNF in the repair effects induced by PRP in an experimental model of osteoarthritis. Initially, the characterization of the PRP obtained was performed, which can be designated as platelet-rich and leukocyte-poor plasma (LPPRP). Later, in our in vitro analysis, it was possible to verify that platelets activated by Ca2+ release BDNF and this suppressed the polarization of M1 macrophages induced by LPS. In ex vivo analyzes performed with animals submitted to the MIA model of OA, it was observed that the Trk-B receptor is involved in the therapeutic effects of LPPRP on the modulation of inflammatory cytokines IL-1? and TNF-?, and on joint damage triggered in the MIA model. In addition, by modulating chronic inflammation in the MIA model, preventing joint degeneration and damage to sensory fibers (coded by reduced expression of the ATF-3 marker), LPPRP treatment was able to promote in vivo functional improvement in animals submitted to OA model, relieving hyperalgesia, and enabling a significant increase in gait parameters that are impaired in the MIA model, such as print area, max contact area, and print width. In addition, Trk-B appears to be essential for the effects of LPPRP, since in the presence of ANA-12 such effects under ATF-3 expression and functional improvement were significantly reversed. Thus, the results indicate that BDNF appears to be essential in the mechanisms of joint repair induced by LPPRP, especially about modulation of inflammation and healing. These findings contribute to clarifying the role of BDNF in joint homeostasis, opening space for the discussion of how molecules typically restricted in their functionality to the central nervous system can also perform repair functions in non-neuronal tissues (AU)

• FAPESP's process: 18/10205-2 - The role of Brain-Derived Neurotrophic Factor (BDNF) in treatment with platelet-rich plasma in experimental model of Osteoarthritis
• Grantee: Kauê Franco Malange
• Support Opportunities: Scholarships in Brazil - Doctorate