The spine journal : official journal of the North American Spine Society · 2025
Effect of casein kinase 1 epsilon on promoting cartilage degeneration in lumbar facet joint osteoarthritis.
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Tan Lixian, He Tianwei, Tang Runmin, Xie Wenwei, Rong Limin, Zhang Liangming
Аннотация
BACKGROUND CONTEXT: 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 OA, but its role in FJOA is unclear.
PURPOSE: To investigate the relationship between CK1ε expression and FJOA severity, and validate its functional role using CK1ε conditional knockout (CKO) mice.
STUDY DESIGN: An experimental study.
METHODS: 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 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).
RESULTS: 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<.001) and inversely with Col II (r=-0.992, p<.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.
CONCLUSIONS: 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.
CLINICAL SIGNIFICANCE: CK1ε is a key promoter of cartilage degeneration in FJOA and a potential therapeutic target for mitigating disease progression.
PURPOSE: To investigate the relationship between CK1ε expression and FJOA severity, and validate its functional role using CK1ε conditional knockout (CKO) mice.
STUDY DESIGN: An experimental study.
METHODS: 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 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).
RESULTS: 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<.001) and inversely with Col II (r=-0.992, p<.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.
CONCLUSIONS: 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.
CLINICAL SIGNIFICANCE: CK1ε is a key promoter of cartilage degeneration in FJOA and a potential therapeutic target for mitigating disease progression.