Abstract
This article provides a brief review of the pathophysiology of osteoarthritis and the ontogeny of chondrocytes and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of autologous chondrocyte implants, matrix-induced autologous chondrocyte implants, and mesenchymal stem cell implants for the successful treatment of damaged articular cartilage and subchondral bone. In response to exercise, articular chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins, and anti-inflammatory cytokines and decrease their production of proinflammatory cytokines and matrix-degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise enhances joint recruitment of bone marrow-derived mesenchymal stem cells and upregulates their expression of osteogenic and chondrogenic genes, osteogenic microRNAs, and osteogenic growth factors. Rodent experiments demonstrate that exercise enhances the osteogenic potential of bone marrow-derived mesenchymal stem cells while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin-1β, tumor necrosis factor-α, and interferon-γ, while increasing their production of antiosteoclastogenic cytokines interleukin-10 and transforming growth factor-β. In conclusion, physical exercise done both by bone marrow-derived mesenchymal stem cell donors and recipients and by autologous chondrocyte donor recipients may improve the outcome of osteochondral regeneration therapy and improve skeletal health by downregulating osteoclastogenic cytokine production and upregulating antiosteoclastogenic cytokine production by circulating immune cells.
Highlights
In the global burden of disease 2010 study, osteoarthritis accounted for 17,135 years of life lived with disability (YLDs), an increase of 64% when compared to YLDs of 1990
In a before and after trial involving 43 healthy adults, Smith and associates measured the effect of six months of combined aerobic, resistance, and flexibility exercises on the production of osteoclastogenic cytokines (IL-1α, tumor necrosis factor (TNF)-α), antiosteoclastogenic cytokines (TGF-β, IL-4, IL-10), and cytokines with variable effects on osteoclastogenesis (interferon (IFN)-γ, IL-6) by cultured mitogenstimulated peripheral blood mononuclear cells (PBMCs)
Sumanasinghe and associates seeded human bone marrow-derived mesenchymal stem cells (BM-MSCs) in 3D type I collagen matrices and subjected them to 0%, 10%, or 12% uniaxial cyclic tensile strain at 1 Hz for 4 h/day for 7 or 14 days. They found that BMP2 mRNA expression and BMP2 production were upregulated in the strain samples as compared to controls, indicating that mechanical strain of the type associated with exercise can induce osteogenic differentiation of human BM-MSCs [49] (Figure 4)
Summary
In the global burden of disease 2010 study, osteoarthritis accounted for 17,135 years of life lived with disability (YLDs), an increase of 64% when compared to YLDs of 1990. In their systematic review of 44 clinical trials involving patients with knee osteoarthritis, Fransen and associates found that land-based therapeutic exercises reduced pain and improved physical function and the quality of life for at least 2–6 months after the cessation of formal treatment [6]. In this regard, the World Health Organization recommends that adult men and women should accumulate at least 150 min of moderate intensity physical exercise per week and young people aged 5–17 years should accumulate at least 60 min of physical exercise of moderate to vigorous intensity daily [7]. I provide an aerobic exercise protocol that can be used to condition tissue donors
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