USP7 Attenuates Endoplasmic Reticulum Stress and NF-κB Signaling to Modulate Chondrocyte Proliferation, Apoptosis,...

Area of Science:

• Biochemistry
• Molecular Biology
• Osteoarthritis Research

Background:

• Chondrocytes are crucial for cartilage health.
• Tumor necrosis factor alpha (TNF-α) induces inflammation in osteoarthritis (OA).
• The role of ubiquitin-specific peptidase 7 (USP7) in OA pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the function and mechanisms of USP7 in chondrocytes during TNF-α-induced inflammation.
• To determine USP7's role in osteoarthritis models.

Main Methods:

• Constructed mouse models of knee osteoarthritis via anterior cruciate ligament transection.
• Assessed USP7 expression using immunohistochemistry.
• Evaluated chondrocyte proliferation, apoptosis, and inflammatory responses after USP7 knockdown or inhibition.
• Utilized western blot, qRT-PCR, ELISA, flow cytometry, and TUNEL staining.
• Investigated signaling pathways including endoplasmic reticulum stress (ERS) and NF-κB/p65 using specific inhibitors and siRNAs.

Main Results:

• USP7 expression was reduced in the knee cartilage of OA mice.
• USP7 knockdown or inhibition decreased chondrocyte proliferation and increased apoptosis and inflammation.
• USP7 inhibition worsened cartilage destruction in OA models.
• USP7 deficiency activated BiP-eIF2α-ATF4-CHOP (ERS) and NF-κB/p65 signaling pathways.
• 4-PBA, si-CHOP, and QNZ partially reversed the effects of USP7 knockdown.

Conclusions:

• USP7 promotes chondrocyte proliferation while suppressing apoptosis and inflammation in TNF-α-induced inflammatory conditions.
• USP7 exerts its protective effects by inhibiting the BiP-eIF2α-ATF4-CHOP (ERS) and NF-κB/p65 signaling pathways.
• USP7 is a potential therapeutic target for osteoarthritis.