Knee Osteoarthritis: Epidemiology, Pathogenesis, and Mesenchymal Stem Cells: What Else Is New? An Update

Abstract

Osteoarthritis (OA) is a chronic disease and the most common orthopedic disorder. A vast majority of the social OA burden is related to hips and knees. The prevalence of knee OA varied across studies and such differences are reflected by the heterogeneity of data reported by studies conducted worldwide. A complete understanding of the pathogenetic mechanisms underlying this pathology is essential. The OA inflammatory process starts in the synovial membrane with the activation of the immune system, involving both humoral and cellular mediators. A crucial role in this process is played by the so-called "damage-associated molecular patterns" (DAMPs). Mesenchymal stem cells (MSCs) may be a promising option among all possible therapeutic options. However, many issues are still debated, such as the best cell source, their nature, and the right amount. Further studies are needed to clarify the remaining doubts. This review provides an overview of the most recent and relevant data on the molecular mechanism of cartilage damage in knee OA, including current therapeutic approaches in regenerative medicine.

Keywords: knee; mesenchymal stem cells; osteoarthritis; pathogenesis; regenerative medicine.

Figure 1

The vicious cycle between synovial membrane and cartilage and the crucial role of “damage-associated molecular patterns” (DAMPs). From the activation of pattern recognition receptors (PRRs) by DAMPs, the cascade of activation of the inflammatory response by synovial fibroblasts and macrophages is initiated. The vicious cycle is sustained by the damage to the ECM caused by the activity of MMPs, which further produce several fragments of molecules working as DAMPs.

Figure 2

Schematic representation of inflammatory mechanisms mediated by different DAMPs. COMP: cartilage oligomeric matrix protein. Receptors: TLR: Toll-like receptor; NLRP3: NOD-like receptor family, pyrin domain containing 3; DDR2: Discoidin domain-containing receptor 2. Signaling pathway: p38: p38 mitogen-activated protein kinases; NF-kB: nuclear factor-kB; MyD88: myeloid differentiation primary response 88. Effects: MMP: matrix metalloproteinase; NO: nitric oxide; IL: interleukin; TNF: tumor necrosis factor.