Background: The characteristics and therapeutic potential of subtypes of mesenchymal stem cells (MSCs) are largely unknown. In this study, CD146⁺and CD146^–MSCs were separated from human umbilical cords, and their effects on regulatory T cells (Tregs), Th17 cells, chondrogenesis, and osteogenesis were investigated.Methods: Flow cytometry was used to quantify IL-6 and TGF-β1 expressed on CD146⁺and CD146^–MSCs. The therapeutic potential of both subpopulations was determined by measuring the clinical score and joint histology after intra-articular (IA) transfer of the cells into mice with collagen-induced arthritis (CIA).Results: Compared with CD146^–MSCs, CD146⁺MSCs expressed less IL-6 and had a significantly greater effect on chondrogenesis. After T lymphocyte activation, Th17 cells were activated when exposed to CD146^–cells but not when exposed to CD146⁺cells bothin vitro and in vivo. IA injection of CD146⁺MSCs attenuated the progression of CIA. Immunohistochemistry showed that only HLA-A⁺CD146⁺cells were detected in the cartilage of CIA mice. These cells may help preserve proteoglycan expression.Conclusions: This study suggests that CD146⁺cells have greater potency than CD146^–cells for cartilage protection and can suppress Th17 cell activation. These data suggest a potential therapeutic application for CD146⁺cells in treating inflammatory arthritis.

Introduction: Accumulation of advanced glycation end products (AGEs) in joints contributes to the pathogenesis of cartilage damage in osteoarthritis (OA). We aim to explore the potential chondroprotective effects of resveratrol on AGEs-stimulated porcine chondrocytes and cartilage explants. Methods: Chondrocytes were isolated from pig joints. Activation of the IκB kinase (IKK)-IκBα-nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)-activator protein-1 (AP-1) pathways was assessed by electrophoretic mobility shift assay (EMSA), Western blot and transfection assay. The levels of inducible nitric oxide synthase (iNOS)-NO and cyclooxygenase-2 (COX-2)-prostaglandin E₂ (PGE₂) were measured by Western blot, Griess reaction or ELISA. The expression and enzyme activity of matrix metalloproteinase-13 (MMP-13) were determined by real time RT/PCR and gelatin zymography, respectively. Results: We show that AGEs-induced expression of iNOS and COX-2 and production of NO and PGE₂ were suppressed by resveratrol. Such effects of resveratrol were likely mediated through inhibiting IKK-IκBα-NF-κB and JNK/ERK-AP-1 signaling pathways induced by AGEs. By targeting these critical signaling pathways, resveratrol decreased AGEs-stimulated expression and activity of MMP-13 and prevented AGEs-mediated destruction of collagen II. Histochemistry analysis further confirms that resveratrol could prevent AGEs-induced degradation of proteoglycan and aggrecan in cartilage explants. Conclusions: The present study reveals not only the effects and mechanisms regarding how resveratrol may protect cartilage from AGEs-mediated damage but also the potential therapeutic benefit of resveratrol in the treatment of OA.

Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease.