The implications of Brain-derived neurotrophic factor in the biological activities of platelet-rich plasma.

Abstract

Platelet-rich plasma (PRP) is a biological blood-derived therapeutic that releases several proteins in injured tissue, regulating the inflammatory process and triggering tissue anabolism. Outside of the central nervous system (CNS), these platelets represent the major source of brain-derived neurotrophic factor (BDNF). The associated anti-inflammatory, antiapoptotic, and antioxidant properties of this neurotrophin could have a potential applicability applied in the pathophysiology of osteoarthritis (OA). In osteoarthritic joints, it is suggested that synovial cells release BDNF, being found higher concentrations of this protein in the patient’s synovial fluid. Thus, considering platelets as an important therapeutic source of BDNF and the potential role of this neurotrophin in regulate joint homeostasis and OA outcomes, this study aimed to evaluate the contribution of BDNF in PRP repair activities on an experimental model of osteoarthritis (EOA) induced by monoiodine acetate (MIA) insult. Initially, the characterization of the PRP was performed, obtaining a leukocyte-poor-platelet-rich plasma (LP-PRP). After, in vitro analysis indicated that platelets activated by Ca2+ release BDNF, and suppression of M1 macrophage polarization induced by LP-PRP is dependent on BDNF-TrkB receptor. The behavioral and ex-vivo analyses in EOA animals showed that functional recovery in gait parameters and mitigation on tissue damage induced by LP-PRP, such as downregulation of inflammatory cytokines (TNF-α), reduction of joint pain and tissue damage (OARSI score and neuronal injury through ATF-3 [+] cells), depends on Trk-B receptor. Thus, the results indicate that BDNF and Trk-B receptor appear to be essential in the mechanisms of joint repair induced by LP-PRP with implications on joint functional recovery as well. These findings contribute to clarifying the role of BDNF in joint homeostasis, repurposing its restricted therapeutic properties in the CNS to repair functions in non-neuronal tissues that could be an option for chronic pain management in osteoarthritis (OA).