Chondrocytes are mechanosensitve cells that respond to changes in the environment to maintain articular cartilage homeostasis. One potential mechanosensitive feedback system involves enzymes and signaling mechanisms that balance the reducing and oxidizing (i.e., “redox”) conditions of the cell.
We found that cyclic compressive loading of healthy bovine cartilage alters the endogenous cartilage antioxidant network. Higher compressive stress (40% strain) increased glutathione oxidation and caused a reduction in the expression of the rate-limiting enzymes for glutathione synthesis. Higher stress also increased the expression of the mitochondrial antioxidant SOD2 while decreasing the cytosolic isoform SOD1, consistent with mitochondrial-derived ROS production at higher loads. Moderate compressive stress (15% strain) caused glutathione oxidation as well, but it also increased total glutathione content and upregulated SOD1 gene expression. Pro-oxidant conditioning of cartilage using tBHP increased glutathione content without altering any other loading-associated changes. These findings suggest that glutathione synthesis, more than antioxidant enzyme upregulation, is a central pro-oxidant and mechanosensitive mediator of antioxidant defense in chondrocytes.
Barboza E, Hudson J, Chang WP, Kovats S, Towner RA, Silasi-Mansat R, Lupu F, Kent C, Griffin TM (2017) Pro-fibrotic infrapatellar fat pad remodeling without M1-macrophage polarization precedes knee osteoarthritis in diet-induced obese mice. Arthritis Rheum. Jan 31. [Epub ahead of print]. [Abstract]
Joint inflammation is an underlying feature of osteoarthritis (OA) pathology, but the role of obesity in this process is poorly understood. Adipose tissue is a critical source of obesity-associated inflammation, and an unresolved question in the field has been whether or not obesity increases the risk of knee OA by inducing inflammation of the infra patellar fat pad (IFP). In this study, we describe our unexpected results of how obesity impacts the IFP.
For the first time, we showed that the IFP does not recapitulate the classic M1-macrophage mediated inflammation that occurs in abdominal adipose tissue with obesity. This protection from obesity-induced inflammation corresponds with the absence of adipocyte hypertrophy and an increase in IFP fibrosis. These data suggest that intra-articular adipocytes are subject to distinct spatial-temporal metabolic regulation among fat pads, possibly due to the structural constraints and cyclic biomechanical stresses associated with joints. Although findings do not support the hypothesis that IFP inflammation is an initiating factor of obesity-induced knee OA, they do show that the IFP is a dynamic joint tissue that remodels with obesity.
This study was highlighted in a recent commentary in Nature Reviews Rheumatology: Ioan-Facsinay, A., & Kloppenburg, M. (2017). Osteoarthritis: Inflammation and fibrosis in adipose tissue of osteoarthritic joints. Nature Reviews Rheumatology, 1–2. http://doi.org/10.1038/nrrheum.2017.53