Platelets Contribute to the Accumulation of Matrix Metalloproteinase Type 2 in Synovial Fluid in Osteoarthritis
Alessia Alunno1, Emanuela Falcinelli2, Filippo Luccioli1
1Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy.
Abstract:
Inflammation plays a role in the initiation and progression of osteoarthritis (OA), a chronic degenerative joint disorder. Platelets are inflammatory cells, contain and release matrix metalloproteinases (MMPs) and favour the release of these enzymes, key effectors of cartilage and subchondral bone degradation, by other cells; however, their role in OA has not been investigated yet. Our aims were (1) to assess the presence of platelets and of MMP-2 in synovial fluid (SF) of OA patients; (2) to evaluate the contribution of platelets to MMP-2 release by fibroblast-like synoviocytes (FLS); and (3) to investigate if hyaluronic acid (HA) interferes with these processes. SF was collected from 27 OA patients before and after treatment with intra-articular HA (20 mg/2 mL). Moreover, FLS were co-cultured with platelets, and the release of MMP-2 in supernatants was measured. Our results show that platelets are present in OA SF and show markers of activation. OA SF also contains relevant amounts of MMP-2. Co-incubation of platelets with FLS favours the release of MMP-2 by the interaction of platelet surface P-selectin with FLS CD44 by a mechanism involving the activation of pAkt and pSrc in FLS. Administration of HA to OA patients decreased the infiltration of platelets in SF and reduced the levels of MMP-2. The addition of HA in vitro inhibited the release of MMP-2 by FLS triggered by the interaction with platelets. In conclusion, our data show that platelets may contribute to joint degeneration in OA by favouring the accumulation of MMP-2 in SF.
Insights
Platelets contribute to osteoarthritis (OA) by releasing matrix metalloproteinases (MMPs) that degrade cartilage. Hyaluronic acid (HA) treatment reduced platelet presence and MMP levels in OA patients, suggesting a therapeutic role.
Area of Science:
- Biochemistry
- Immunology
- Orthopedics
Background:
- Osteoarthritis (OA) is a degenerative joint disease where inflammation plays a key role.
- Platelets, known inflammatory cells, release matrix metalloproteinases (MMPs) implicated in cartilage and bone degradation.
- The specific role of platelets in OA pathogenesis remained uninvestigated.
Purpose of the Study:
- To determine the presence of platelets and MMP-2 in osteoarthritis synovial fluid (SF).
- To evaluate platelet contribution to MMP-2 release by fibroblast-like synoviocytes (FLS).
- To investigate the effect of hyaluronic acid (HA) on these OA-related processes.
Main Methods:
- Synovial fluid (SF) was collected from 27 OA patients before and after intra-articular HA treatment.
- Fibroblast-like synoviocytes (FLS) were co-cultured with platelets to measure MMP-2 release.
- Platelet presence, activation markers, MMP-2 levels, and signaling pathways (pAkt, pSrc) were analyzed.
Main Results:
- Activated platelets and significant MMP-2 levels were detected in OA SF.
- Platelet-FLS co-incubation enhanced MMP-2 release via P-selectin/CD44 interaction, activating FLS pAkt and pSrc.
- HA treatment reduced platelet infiltration and MMP-2 levels in OA SF and inhibited platelet-induced MMP-2 release in vitro.
Conclusions:
- Platelets are present and activated in OA synovial fluid, contributing to MMP-2 accumulation.
- Platelet-FLS interaction promotes MMP-2 release, potentially driving joint degeneration in OA.
- Intra-articular hyaluronic acid demonstrates a therapeutic potential by mitigating platelet-driven MMP-2 release in OA.
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