Selenoprotein S Deficiency Induces Matrix Degradation Via TGF-β Pathway Leading to Cartilage Damage

Area of Science:

• Biochemistry
• Cell Biology
• Nutritional Science

Background:

• Selenium is an essential trace element crucial for human health, functioning via selenoproteins.
• Selenoproteins are vital for bone and cartilage development, with Selenoprotein S (SelS) roles in oxidative stress and inflammation needing further clarification.
• Cartilage matrix degradation is a hallmark of fibrotic and degenerative joint diseases.

Purpose of the Study:

• To investigate the impact of Selenoprotein S (SelS) deficiency on cartilage matrix degradation.
• To elucidate the role of SelS in maintaining cartilage homeostasis.
• To explore the involvement of the TGF-β signaling pathway in SelS-deficiency-induced cartilage damage.

Main Methods:

• Constructed chondrocytes with SelS gene knockdown (sh-Sels) and SelS gene knockout mice.
• Quantified mRNA and protein levels of collagen type II (COL II) and matrix metalloproteinases (MMP3, MMP10, MMP13) using RT-qPCR and Western blotting.
• Assessed cartilage morphology and composition via histological staining (toluidine blue, safranin O-fast green, sirius red) and immunohistochemistry (IHC).

Main Results:

• SelS deficiency decreased COL II levels and increased MMP3, MMP10, and MMP13 expression in chondrocytes.
• SelS knockout mice exhibited reduced proteoglycan and collagen content, decreased COL II, and increased MMP3, MMP13, and MMP19 in articular cartilage.
• Inhibition of the TGF-β pathway partially restored Col2a1 expression in SelS-deficient chondrocytes.

Conclusions:

• SelS is essential for maintaining cartilage homeostasis and preventing matrix degradation.
• SelS deficiency contributes to cartilage matrix degradation, partly through the TGF-β signaling pathway.
• Targeting selenoproteins, like SelS, presents a potential therapeutic strategy for fibrotic and degenerative cartilage diseases.