Researchers from Chongqing Medical University and New York University School of Medicine recently published a research paper entitled "XBP1S Associates with RUNX2 and Regulates Chondrocyte Hypertrophy", confirming that XBP1S regulates chondrocyte hypertrophy by acting as a cofactor for Runx2 and affecting IHH / PTHrP signaling . Related results were published in the Journal of Biochemistry (JBC).

The corresponding author of the article is Professor Guo Fengjin of Chongqing Medical University. Mainly engaged in the research of the molecular genetic mechanism of cartilage and osteogenesis, and achieved a series of innovative achievements in chondrocyte differentiation, chondrocyte injury and repair, and the mechanism of action of inflammatory factors. Published more than 30 papers in well-known academic journals at home and abroad, including "SCIENCE", "FASEB Journal", "Arthritis Rheumatism", "Cellular Signalling", among which 10 were included in SCI.

It is well known that bone morphogenetic protein 2 (BMP2) can activate unfolded protein response (UPR) signaling molecules, including XBP1S and ATF6. However, the effect of BMP2-induced chondrocyte differentiation on XBP1S and ATF6 remains to be elucidated.

In this article, the researchers confirmed that BMP2 mediates mild ER pressure activation of ATF6 during cartilage formation and directly regulates XBP1S splicing. XBP1S was differentially expressed during the chondrocyte differentiation process stimulated by BMP2, and showed significant expression in growth plate chondrocytes. This expression may be due to the activation of XBP1 gene by ATF6 and the induction of splicing by IRE1a. ATF6 directly binds to the 5 "-flanking regulatory region of XBP1 gene.

Overexpression of XBP1S promoted the expression of type II Collagen, ype X Collagen, and Runx2, indicating accelerated chondrocyte hypertrophy. Conversely, using RNA interference (RNAi) to inhibit XBP1S can eliminate hypertrophic chondrocyte differentiation. In addition, the researchers confirmed that XBP1S combined with Runx2 promotes Runx2-mediated chondrocyte hypertrophy. The changes of Indian hedgehog factor (IHH) and parathyroid hormone related peptide (PTHrP) in chondrocyte hypertrophy are accompanied by changes in XBP1S expression.

The above results confirmed that XBP1S regulates chondrocyte hypertrophy by acting as a cofactor for Runx2 and affecting IHH / PTHrP signaling. XBP1S is a new regulator in a complex network that regulates pre-hypertrophy, hypertrophy and differentiation of growth plate chondrocytes.

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