CypD-mPTP axis regulates mitochondrial functions contributing to osteogenic dysfunction of MC3T3-E1 cells in inflammation

Bone is a dynamic organ, the bone-forming osteoblasts and bone-resorbing osteoclasts form the physiological basis of bone remodeling process. During pathological process of numerous inflammatory diseases, these two aspects are uncoupled and the balance is usually tipped in favor of bone destruction. Evidence suggests that the inflammatory destruction of bone is mainly attributed to oxidative stress and is closely related to mitochondrial dysfunction. The mechanisms underlying osteogenic dysfunction in inflammation still need further investigation. Reactive oxygen species (ROS) is associated with mitochondrial dysfunction and cellular damage. Here, we reported an unexplored role of cyclophilin D (CypD), the major modulator of mitochondrial permeability transition pore (mPTP), and the CypD-mPTP axis in inflammation-induced mitochondrial dysfunction and bone damage. And the protective effects of knocking down CypD by siRNA interference or the addition of cyclosporin A (CsA), an inhibitor of CypD, were evidenced by rescued mitochondrial function and osteogenic function of osteoblast under tumor necrosis factor-alfa (TNF-alfa) treatment. These findings provide new insights into the role of CypD-mPTP-dependent mitochondrial pathway in the inflammatory bone injury. The protective effect of CsA or other moleculars affecting the mPTP formation may hold promise as a potential novel therapeutic strategy for inflammation-induced bone damage via mitochondrial pathways

Influence of a Streptomyces lividans SecG functional analogue on protein secretion

The membrane protein complex translocase mediates the translocation of bacterial proteins. In this complex, the SecY, SecE, and SecG proteins constitute an integral membrane domain. Sequence comparison revealed a potential secG-like gene in the gram-positive soil bacterium Streptomyces lividans. Chromosomal deletion of this gene resulted in a sporulation defect and an overall deficiency in secretion. The SecG-depleted strain was able to overproduce and secrete alpha-amylase, but the appearance of the oversynthesized protein outside the cell was delayed compared to the protein produced by the wildtype strain. SecG deficiency was found to result in more pronounced effects in S. lividans than in Bacillus subtilis or Escherichia coli (AU)

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