Variance of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) concentrations in activated, concentrated platelets from healthy male donors

Abstract

BackgroundThe use of autologous blood concentrates, such as activated, concentrated platelets, in orthopaedic clinical applications has had mixed results. Research on this topic has focused on growth factors and cytokines, with little directed towards matrix metalloproteinases (MMPs) which are involved in post-wound tissue remodeling.MethodsIn this study, the authors measured the levels of MMP-2, MMP-9 and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), in activated platelets derived from blood of healthy, male volunteers (n = 92), 19 to 60 years old. The levels of the natural inhibitors of these proteases, tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP-2 and TIMP-4 were also assessed.ResultsNotably, there was no significant change in concentration with age in four of six targets tested. However, TIMP-2 and TIMP-4 demonstrated a statistically significant increase in concentration for subjects older than 30 years of age compared to those 30 years and younger (P = 0.04 and P = 0.04, respectively).ConclusionTIMP-2 and TIMP-4 are global inhibitors of MMPs, including MMP-2 (Gelatinase A). MMP-2 targets native collagens, gelatin and elastin to remodel the extracellular matrix during wound healing. A decreased availability of pharmacologically active MMP-2 may diminish the effectiveness of the use of activated, concentrated platelets from older patients, and may also contribute to longer healing times in this population.

Hypoxia and matrix viscoelasticity sequentially regulate endothelial progenitor cluster-based vasculogenesis

“…The lowest concentration of MMP (1 g/ml) yielded sprouting reminiscent of classical single-cell vasculogenesis but no cluster formation. These results suggest that an unprecedented concentration of MMPs is required for cluster formation compared with those analyzed from patient samples and those typically associated with classical single-cell vasculogenesis (49)(50)(51)(52)(53).…”

Matrix metalloproteinases 2 and 9 activity after intra-articular injection of autologous platelet-rich plasma for the treatment of osteoarthritis in dogs

“…Zymography gives information on the identification of the MMPs and the relative amounts of the enzymes present. The MMPs degrade gelatin, collagen, elastin, aggrecan, osteonectin, cytokines, growth factors, and receptors (Hire et al 2014). These molecules initiate chemotactic gradients, regulate inflammation, and extravasation of leukocytes into injured tissue (Gill and Parks 2008).…”

The Use of Dehydrated Human Amnion/Chorion Membrane Allograft Injection for the Treatment of Tendinopathy or Arthritis: A Case Series Involving 40 Patients

“…Second, both the absolute concentration as well as the relative ratio of the growth factors, cytokines, and tissue inhibitors of metalloproteinases differs between PRP and dHACM. Variation in PRP may be due to the preparation method as well as to patient factors such as age and concomitant NSAID use [28,29]. Because the effect of both of these treatments relies on a dynamic and complex interplay of cell signaling and anabolic and catabolic cascades, the differences between the active biologic components in PRP and dHACM present a rich opportunity for further study.…”