Mitochondrial Transplantation Ameliorates the Development and Progression of Osteoarthritis

Abstract

Osteoarthritis (OA) is a common degenerative joint disease characterized by breakdown of joint cartilage. Mitochondrial dysfunction of the chondrocyte is a risk factor for OA progression. We examined the therapeutic potential of mitochondrial transplantation for OA. Mitochondria were injected into the knee joint of monosodium iodoacetate-induced OA rats. Chondrocytes from OA rats or patients with OA were cultured to examine mitochondrial function in cellular pathophysiology. Pain, cartilage destruction, and bone loss were improved in mitochondrial transplanted-OA rats. The transcript levels of IL-1β, TNF-α, matrix metallopeptidase 13, and MCP-1 in cartilage were markedly decreased by mitochondrial transplantation. Mitochondrial function, as indicated by membrane potential and oxygen consumption rate, in chondrocytes from OA rats was improved by mitochondrial transplantation. Likewise, the mitochondrial function of chondrocytes from OA patients was improved by coculture with mitochondria. Furthermore, inflammatory cell death was significantly decreased by coculture with mitochondria. Mitochondrial transplantation ameliorated OA progression, which is caused by mitochondrial dysfunction. These results suggest the therapeutic potential of mitochondrial transplantation for OA.

Effects of mitochondrial dysfunction on bone metabolism and related diseases: a scientometric study from 2003 to 2022

“…Future research in this area will focus on the factors leading to mitochondrial dysfunction, including oxidative stress, aging, gene expression, and the pathogenesis of bone metabolism-related diseases. The clinical implications of the current scientometric analysis could help us explore some potential treatment directions such as regulating inflammatory, catabolic factors, and mitochondrial transplantation for bone metabolic diseases [ 49 ].…”

Mitochondrial dysfunction: mechanisms and advances in therapy

“… 426 Similarly, the progression of osteoarthritis induced by monosodium iodoacetate was significantly inhibited by mitochondria from the skeletal (L6) myoblast cell line, which was also supported by improved pain phenotypes. 427 Intravenous administration of mtDNA and TFAM mRNA-containing MSC-EVs was effective in reducing mitochondrial damage and inflammatory response in acute renal injury. This was possibly due to the protection of mitochondria in stressed HK-2 cells by TFAM-induced mtDNA maintenance.…”

“…Studies on other diseases also illustrated the protective effect of mitochondrial transplantation, ranging from wound healing capacity to multiple sclerosis, tendinopathy, and osteoarthritis. [424][425][426][427] Mitochondria from platelets were reported to stimulate the angiogenic potential of MSCs, thus promoting wound healing and tissue repair in chronic muscle injury. 424 The directly administered mitochondria enhanced the TCA cycle and fatty acid synthesis, which was previously reported to favor epithelial cell proliferation for angiogenesis.…”

Mitochondrial transplantation and transfer: The promising method for diseases

“…Osteoarthritis (OA) progression is at risk due to chondrocyte mitochondrial dysfunction. In OA animals with mitochondrial transplants, there was a reduction in pain, cartilage degradation, bone loss, and mitochondrial transplantation significantly reduced the transcript levels of inflammation (IL-1, tumor necrosis factor-alpha (TNF-)), chemokines (matrix metallopeptidase 13, monocyte chemoattractant protein-1 (MCP-1)) ( Lee et al, 2022 ). Because of its advantages such as decreasing oxidative stress, and increasing regeneration, mitochondrial transplantation could serve as one of the future therapy strategies for skeletal muscle problems.…”