Knockdown of LMX1B Suppressed Cell Apoptosis and Inflammatory Response in IL-1β-Induced Human Osteoarthritis Chondrocytes through NF-κB and NLRP3 Signal Pathway

Abstract

Osteoarthritis (OA), a chronic degenerative joint disease, always occurred in the aging population. There is evidence suggests that chondrocytes’ survival, inflammation, and apoptosis play critical roles in OA pathogenesis. LMX1B has been shown to be involved in antiosteogenic function in early patterning of the calvaria. However, the role and mechanism of LMX1B in OA is not unknown. The present study observed that LMX1B was highly expressed in OA patients compared with normal patients. Besides, we found that IL-1β increased LMX1B mRNA and protein expression in SW1353 and C28/I2 chondrocytes. LMX1B knockdown increased IL-1β-induced cell viability and proliferation and suppressed cell apoptosis and inflammation response, including IFN-γ, TNF-α, IL-6, prostaglandin E2 (PGE2), and NO both in SW1353 and C28/I2. Furthermore, LMX1B silence inhibited MMP-3 and MMP-13 expression both in SW1353 and C28/I2 cells. Also, the activation of the NF-κB and NLRP3 signaling pathway was suppressed in LMX1B silence cells by decreasing the p-p65 and NLRP3 protein expressions. Additionally, inhibition of NF-κB by PDTC suppressed NLRP3 expression. Moreover, NLRP3 overexpression reversed the effects of LMX1B silence on chondrocytes’ survival, proliferation, apoptosis, and inflammation. Finally, we confirmed that LMX1B depletion had protective effects in OA rats in vivo.

The first presentation of a case of nail-patella syndrome newly diagnosed at the onset of rheumatoid arthritis: a case report

“…Loss-of-function variations in LARM1/2 genes have been identified in NPS patients with a normal LMX1B coding sequence [ 17 ]. Some of the musculoskeletal manifestations observed in NPS are common in RA, while knockdown of LMX1B has been reported to have a protective effect on osteoarthritis [ 18 ], and a genetic link between LMX1B and RA has not been reported. Although we did not perform a genetic test since the patient did not agree with the test, the physical and radiographic findings as well as dysplasia of bilateral thumb nails of both the patient and his sister were conclusively consistent with the diagnosis of NPS.…”

Arthralgia and joint deformity, rheumatoid arthritis? or nail-patella syndrome?

“…RA is a chronic autoimmune inflammatory disorder that causes joint inflammation and destruction. Knockdown of LMX1B has been reported to have a protective effect on osteoarthritis, 15 while a genetic link between LMX1B and RA has yet to be reported. In addition to arthralgia and joint deformity, multi-organ involvement including neurological abnormality, open-angle glaucoma and glomerulonephritis due to systemic inflammation are observed in patients with RA, 1 indicating that both NPS and RA share some clinical features and similar organ involvements, although the pathogenesis and prognosis of NPS and those of RA are different.…”

Mechanism of NLRP3 inflammasome intervention for synovitis in knee osteoarthritis: A review of TCM intervention

“…Subsequently, Pro-caspase-1 is self-sheared and activated to Caspase-1 p10 and Caspase-1 p20. After Caspase-1 is activated, pro-IL-1β and pro-IL-18 can be sheared into mature IL-1β and IL-18 ( Li et al, 2021 ; Mu et al, 2022 ; Zhang et al, 2022 ; Zhang et al, 2018 ; Pei et al, 2022 ). Then released to the outside of the cell, and more inflammatory cells (HMGB1, leukotrienes, prostaglandins, etc.)…”