Biochimica et biophysica acta. Molecular basis of disease · 2025
CXCL8 and GZMB genes promote cartilaginous and synovial lesion formation via NF-κB and MAPK signaling pathways in Kaschin-Beck disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Cai Dechao, Hu Zhongyao, Zhu Yakun, Ma Xiao, Wang Changming, Wang Chen, Bian Ashuai, Zhang Haotian, He Junyan, LunZhu CiRen, Yu Haoran, Cheng Wendan
Аннотация
BACKGROUND: Kaschin-Beck disease (KBD), which is endemic to Russia, North Korea, Sichuan Province, and the Tibet Autonomous Region of China, seriously affects patient health. Its pathogenesis remains unclear, treatment limited, and prognosis poor. Thus, clarifying its pathogenesis and identifying biomarkers for its diagnosis and treatment are vital.
METHODS: Differentially expressed genes (DEGs) and their potential roles in KBD were identified using RNA sequencing of articular cartilage and synovial tissue samples from patients with KBD versus osteoarthritis (OA). A weighted gene co-expression network analysis (WGCNA) identified disease-related gene modules, while a protein-protein interaction (PPI) network identified key genes. Finally, quantitative reverse transcription polymerase chain reaction and western blotting evaluated the expression and pathogenesis of the core genes in the cartilage and synovium in KBD.
RESULTS: Compared to those from patients with OA, cartilage and synovium samples from patients with KBD exhibited 869 and 2132 DEGs, respectively. In the WGCNA of KBD, the red, brown, and yellow modules showed the highest correlation with cartilage lesions, whereas the antiquewhite2 and firebrick4 modules showed the highest correlation with synovial lesions. The PPI network of KBD revealed CXCL8 and granzyme B (GZMB) as core genes in cartilaginous and synovial lesions, respectively; their overexpressions can activate the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, respectively, and promote inflammatory factor release in chondrocytes and synovial fibroblasts.
CONCLUSION: Our results provide new insight into the potential molecular mechanisms underlying KBD and identified molecular markers possibly contributing to its future early diagnosis and clinical treatment.
METHODS: Differentially expressed genes (DEGs) and their potential roles in KBD were identified using RNA sequencing of articular cartilage and synovial tissue samples from patients with KBD versus osteoarthritis (OA). A weighted gene co-expression network analysis (WGCNA) identified disease-related gene modules, while a protein-protein interaction (PPI) network identified key genes. Finally, quantitative reverse transcription polymerase chain reaction and western blotting evaluated the expression and pathogenesis of the core genes in the cartilage and synovium in KBD.
RESULTS: Compared to those from patients with OA, cartilage and synovium samples from patients with KBD exhibited 869 and 2132 DEGs, respectively. In the WGCNA of KBD, the red, brown, and yellow modules showed the highest correlation with cartilage lesions, whereas the antiquewhite2 and firebrick4 modules showed the highest correlation with synovial lesions. The PPI network of KBD revealed CXCL8 and granzyme B (GZMB) as core genes in cartilaginous and synovial lesions, respectively; their overexpressions can activate the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, respectively, and promote inflammatory factor release in chondrocytes and synovial fibroblasts.
CONCLUSION: Our results provide new insight into the potential molecular mechanisms underlying KBD and identified molecular markers possibly contributing to its future early diagnosis and clinical treatment.