Reduced autophagy has been implied in chondrocyte death and osteoarthritis. Curcumin (Cur) owns therapeutic effect against osteoarthritis (OA) and enhances autophagy in various tumor cells. Whether the cartilage protection of curcumin is associated with autophagy promotion and the potential signaling pathway involved remains unclear. The present study aimed to investigate the role of autophagy in the anti-OA activity of curcumin using spontaneous and surgically induced OA mice model. Spontaneous and surgically induced OA mice model was established and treated with Cur. Articular cartilage destruction and proteoglycan loss were scored through Safranin O/Fast green staining. Apoptotic cell death was detected with TUNEL (terminal deoxynucleotidyl transferase-mediated dTUP-biotin nick end labeling assay) staining and Western blot for caspase-3, Bcl-2 associated X protein (Bax), and Bcl-2 (B-cell lymphoma-2). Light chain 3 (LC3) immunohistochemistry was used to evaluate autophagy. In vitro, primary chondrocytes were treated with interleukin 1 beta (IL-1β) and Cur. Autophagy was inhibited using 3-methyladenine. Apoptosis and autophagy were detected using flow cytometry and Western blotting assay. Curcumin treatment enhanced autophagy, reduced apoptosis, and cartilage loss in both OA models. In vitro, curcumin treatment improved IL-1β induced autophagy inhibition, cell viability decrease, and apoptosis. Mechanistically, in vivo studies suggested curcumin promoted autophagy through regulating Akt/mTOR pathway. In conclusion, our results demonstrate that curcumin-induced autophagy via Akt/mTOR signaling pathway contributes to the anti-OA effect of curcumin.

The adult mammalian CNS has a limited capacity to regenerate after traumatic injury. In this study, a combinatorial strategy to promote axonal regeneration and functional recovery after spinal cord injury (SCI) was evaluated in adult rats. The rats were subjected to a complete transection in the thoracic spinal cord, and multichannel scaffolds seeded with activated Schwann cells (ASCs) and/or rat bone marrow-derived mesenchymal stem cells (MSCs) were acutely grafted into the 3-mm-wide transection gap. At 4 weeks posttransplantation and thereafter, the rats receiving scaffolds seeded with ASCs and MSCs exhibited significant recovery of nerve function as shown by the Basso, Beattie and Bresnahan (BBB) score and electrophysiological test results. Immunohistochemical analyses at 4 and 8 weeks after transplantation revealed that the implanted MSCs at the lesion/graft site survived and differentiated into neuron-like cells and co-localized with host neurons. Robust bundles of regenerated fibers were identified in the lesion/graft site in the ASC and MSC co-transplantation rats, and neurofilament 200 (NF) staining confirmed that these fibers were axons. Furthermore, myelin basic protein (MBP)-positive myelin sheaths were also identified at the lesion/graft site and confirmed via electron microscopy. In addition to expressing mature neuronal markers, sparse MSC-derived neuron-like cells expressed choline acetyltransferase (ChAT) at the injury site of the ASC and MSC co-transplantation rats. These findings suggest that co-transplantation of ASCs and MSCs in a multichannel polymer scaffold may represent a novel combinatorial strategy for the treatment of spinal cord injury.

After spinal cord injury (SCI), destruction of the blood spinal cord barrier (BSCB) results in in ltration of blood cells, such as neutrophils and macrophages, leading to permanent neurological dysfunction.Previous studies have shown that human bone marrow mesenchymal stem cell (BMSC)-derived exosomes have a bene cial neuroprotective effect in SCI models. However, whether BMSC-Exos contribute to the integrity of the BSCB has not been clari ed. The purpose of this study was to investigate the mechanism of BMSC-Exo-induced changes in the permeability of the BSCB after SCI. Here, we showed that BMSC-Exos can inhibit BSCB permeability damage and improve spontaneous repair in a SCI model. Importantly, tissue inhibitors of matrix metalloproteinases 2 (TIMP2) were shown to play an important role in the functions of BMSCS-Exos by inhibiting the matrix metalloproteinase (MMP) pathway, thereby mitigating the reduction in cell junction proteins. Moreover, the ability of BMSC-Exos was signi cantly attenuated when TIMP2 was inhibited by siRNA. This proof-of-principle study demonstrates that BMSC-Exos can preserve the integrity of the BSCB and improve functional recovery after SCI through the TIMP2/MMP signaling pathway.