Abstract
Platelets and their secretory products play an important role in determining the balance between tissue repair and tissue damage. To obtain novel insights into the molecular composition of platelet-rich plasma (PRP) and contextualize them in knee osteoarthritis (OA), two different plasma formulations, namely PRP and platelet-poor plasma (PPP), were prepared from six healthy donors following a biobank-automated protocol. Inter-donor differences were analyzed, and pools were created before performing multiplexing protein arrays. In addition, PRP and PPP were prepared from six patients following our in-house protocols. Supernatants from PRP and PPP were harvested one hour after calcium chloride activation. Multiplexing protein arrays were performed in parallel for all plasma formulations. Results were normalized to fold change in relation to PPP and examined using Ingenuity Pathway Analysis Software. Bioinformatic predictions showed that PRPs constitute a signaling system with interrelated networks of inflammatory and angiogenic proteins, including but not limited to interleukin-6 and -8 (IL-6, IL-8), insulin like growth factor 1 (IGF-1), transforming growth factor beta, (TGF-b), and vascular endothelial growth factor (VEGF) signaling, underlying biological actions. Predictions of canonical systems activated with PRP molecules include various inflammatory pathways, including high-mobility group box protein (HMGB1) and interleukin 17 (IL-17) signaling, neuroinflammation, and nuclear factor-kappa b (NF-κB) pathways. Eventually, according to these predictions and OA evolving knowledge, selected PRP formulations should be tailored to modulate different inflammatory phenotypes, i.e., meta-inflammation, inflame-aging or posttraumatic inflammatory osteoarthritis. However, further research to discriminate the peculiarities of autologous versus allogeneic formulations and their effects on the various OA inflammatory phenotypes is needed to foster PRPs.
Highlights
Osteoarthritis (OA) is a common incurable disease with pain, joint stiffness, and progressive impaired mobility as the predominant symptoms
We studied the levels of human RANTES (CCL5) (900-K33; Peprotech Inc., Rocky Hill, NJ, USA), human vascular endothelial growth factor (VEGF) (900-K10; Peprotech Inc., Rocky Hill, NJ, USA), human MCP-1 (CCL2) (900-K31, Peprotech Inc., Rocky Hill, NJ, USA), human PDGF-BB (900-K04, Peprotech Inc, Rocky Hill, NJ, USA), and human PF4 (CXCL4) in platelet-rich plasma (PRP) and platelet-poor plasma (PPP)
We evaluated the data set obtained from the multiplexing platform in the context of a large, structured collection of observations in various experimental settings with nearly 5 million findings manually curated from the biomedical literature or integrated from third-party databases, using the Ingenuity Pathway Analysis Software (IPA; Qiagen, Redwoood City, CA, USA)
Summary
Osteoarthritis (OA) is a common incurable disease with pain, joint stiffness, and progressive impaired mobility as the predominant symptoms. The prevalence of OA has doubled when comparing the pre- and post-industrial periods, even after controlling for main risk factors, i.e., obesity and ageing [1]. In the current context of demographic changes and pandemia, the pace of baby boomers undergoing retirement has accelerated the need of OA effective treatments to avoid joint failure, pain, and disability, eventually ending in knee replacement [5]. The latter is predicted to rise 855% by 2012–2050 [6], with half of the recipients under 65 years. These patients spend an average of 13 years in palliative treatments [7]
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