Arthritis & rheumatology (Hoboken, N.J.)
-
Arthritis Rheumatol · May 2015
Articular ankle fracture results in increased synovitis, synovial macrophage infiltration, and synovial fluid concentrations of inflammatory cytokines and chemokines.
The inflammatory response following an articular fracture is thought to play a role in the development of posttraumatic arthritis (PTA) but has not been well characterized. The objective of this study was to characterize the acute inflammatory response, both locally and systemically, in joint synovium, synovial fluid (SF), and serum following articular fracture of the ankle. We hypothesized that intraarticular fracture would alter the synovial environment and lead to increased local and systemic inflammation. ⋯ Articular fracture of the ankle increased acute local inflammation, as indicated by increased synovitis, increased macrophage infiltration into synovial tissue, and increased SF concentrations of biomarkers of inflammation. Characterizing the acute response to articular fracture provides insight into the healing process and may help to identify patients who may be at greater risk of PTA.
-
Arthritis Rheumatol · May 2015
Mitochondrial biogenesis is impaired in osteoarthritis chondrocytes but reversible via peroxisome proliferator-activated receptor γ coactivator 1α.
The etiology of chondrocyte mitochondrial dysfunction in osteoarthritis (OA) is not completely understood. OA chondrocytes are deficient in the metabolic biosensors active AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT-1), which modulate the mitochondrial biogenesis "master regulator" peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). Moreover, PGC-1α critically mediates AMPK anticatabolic activity in chondrocytes. The aim of this study was to test the hypothesis that mitochondrial biogenesis is deficient in human OA chondrocytes and that this deficiency functionally increases chondrocyte procatabolic responses, which are reversed by activation of the AMPK/SIRT-1/PGC-1α pathway. ⋯ Mitochondrial biogenesis is deficient in human OA chondrocytes, and this deficiency promotes chondrocyte procatabolic responses. TFAM-mediated activation of the AMPK/SIRT-1/PGC-1α pathway reverses these effects, suggesting translational potential of pharmacologic AMPK activators to limit OA progression.
-
Arthritis Rheumatol · May 2015
Randomized Controlled TrialCognitive-behavioral therapy for insomnia in knee osteoarthritis: a randomized, double-blind, active placebo-controlled clinical trial.
Insomnia is prevalent among patients with knee osteoarthritis (OA). Research indicates that sleep disruption may amplify clinical pain by altering central pain modulation, suggesting that treatment of insomnia may improve pain. The aims of this study were to evaluate the efficacy of cognitive-behavioral therapy for insomnia (CBT-I) in patients with knee OA, to determine whether improvements in sleep predict reduced pain, and to determine whether alterations in pain modulation mediate improvements in clinical pain. ⋯ Compared with active placebo, CBT-I was efficacious in reducing sleep maintenance insomnia. CBT-I decreased clinical pain, but not pain modulation, suggesting that it has the potential to augment pain management in knee OA. Future work is needed to identify the mechanisms by which improved sleep reduces clinical pain.
-
Arthritis Rheumatol · May 2015
Randomized Controlled TrialEfficacy and safety of etanercept in patients with the enthesitis-related arthritis category of juvenile idiopathic arthritis: results from a phase III randomized, double-blind study.
To evaluate the efficacy and safety of etanercept in patients with enthesitis-related arthritis (ERA) in juvenile idiopathic arthritis (JIA). ⋯ In this study of patients with the ERA category of JIA, etanercept proved effective, as indicated by high ACR Pedi response rates and JADAS10 response rates at week 24. Patients who continued treatment with etanercept had significantly fewer flares than those who received placebo, although 50% of patients in the placebo group did not experience a flare. Treatment suspension may be a consideration for patients with the ERA category of JIA who achieve remission.
-
Arthritis Rheumatol · May 2015
Use of recombinant human stromal cell-derived factor 1α-loaded fibrin/hyaluronic acid hydrogel networks to achieve functional repair of full-thickness bovine articular cartilage via homing of chondrogenic progenitor cells.
Articular cartilage damage after joint trauma seldom heals and often leads to osteoarthritis. We previously identified a migratory chondrogenic progenitor cell (CPC) population that responds chemotactically to cell death and rapidly repopulates the injured cartilage matrix, which suggests a potential approach for articular cartilage repair. This study was undertaken to determine whether recombinant human stromal cell-derived factor 1α (rhSDF-1α), a potent CPC chemoattractant, would improve the quality of cartilage regeneration, hypothesizing that increased recruitment of CPCs by rhSDF-1α would promote the formation of cartilage matrix upon chondrogenic induction. ⋯ This study showed that stimulating local CPC recruitment prior to treatment with chondrogenic factors significantly improves the biochemical and mechanical properties of the cartilage tissue formed in chondral defects. This simple approach may be implemented in vivo as a one-step procedure by staging the release of chemokine and chondrogenic factors from within the hydrogel, which can be achieved using smart drug-delivery systems.