Effect of Casein Kinase 1 epsilon on promoting cartilage degeneration in lumbar facet joint osteoarthritis.

Abstract

Lumbar facet joint osteoarthritis (FJOA) is a major cause of low back pain, yet its molecular mechanisms remain poorly understood. Casein Kinase 1 epsilon (CK1ε) has been implicated in osteoarthritis, but its role in FJOA is unclear. To investigate the relationship between CK1ε expression and FJOA severity, and validate its functional role using CK1ε conditional knockout mice. An experimental study. Human facet joint cartilage specimens were obtained from FJOA patients (Pathria grade 2-3) and controls (scoliosis patients, Pathria grade 0-1). CK1ε, matrix metallopeptidase 13 (MMP13), and collagen (Col) I, II, X expression were evaluated via immunofluorescence, immunohistochemistry, and Western blot. For in vivo validation, wild-type and CK1ε conditional knockout (CKO) mice underwent unilateral facet joint osteotomy to induce FJOA. Cartilage degeneration was assessed histologically (OARSI score) and molecularly (CK1ε, JNK/p-JNK, MMP13 expression). In human FJOA cartilage, CK1ε and MMP13 were significantly upregulated, while Col II decreased and Col I and Col X increased. CK1ε expression strongly correlated with Pathria grade (r = 0.973, P < 0.001) and inversely with Col II (r = -0.992, P < 0.001). In mice, osteotomy-induced FJOA increased CK1ε, MMP13, and p-JNK expression, and severe cartilage degeneration was observed. CKO mice showed protection against cartilage damage, with near-normal OARSI scores and reduced expression of degenerative markers. CK1ε is upregulated in FJOA and strongly correlates with degeneration severity. It promotes cartilage breakdown via JNK pathway activation. Genetic inhibition of CK1ε attenuates FJOA progression in mice. CK1ε is a key promoter of cartilage degeneration in FJOA and a potential therapeutic target for mitigating disease progression.