Research Article: CORO1A links inflammatory chondrocyte subpopulations to immune microenvironment alterations in osteoarthritis: an integrative multi-omics and single-cell study
Abstract:
Osteoarthritis (OA) is increasingly understood as a condition influenced by the diversity of chondrocytes and immune system dysfunction; however, the specific molecular elements connecting distinct chondrocyte populations to the immune environment remain inadequately explored. The protein CORO1A, associated with the cytoskeleton and implicated in immune regulation, has not been thoroughly investigated in the context of OA or through single-cell analysis.
We employed multi-omics techniques alongside single-cell RNA sequencing, supported by experimental validation using human OA cartilage samples, a murine model of medial meniscus destabilization (DMM), and in vitro inflammatory chondrocyte models to elucidate the expression patterns and functional significance of CORO1A in OA.
The CORO1A gene is recognized as significantly expressed in osteoarthritic cartilage. Transcriptomic evaluations reveal that CORO1A is predominantly expressed in inflammatory and proliferative chondrocyte subpopulations, while showing lower levels in other chondrocyte types, underscoring the specificity of these groups. The upregulation of CORO1A is associated with increased infiltration of various immune cells, including M2 macrophages, plasma cells, and natural killer cells, and is linked to the activation of IL-6/JAK-STAT3 and TNF-?/NF-?B signaling pathways. Additionally, experimental data indicate that CORO1A is markedly elevated in the cartilage regions affected by osteoarthritis in both humans and mice. In terms of its function, the expression of CORO1A in primary chondrocytes is enhanced by inflammatory stimuli, while its suppression leads to reduced MMP13 expression and diminished chondrocyte migration. Conclusion: This study identifies CORO1A as a regulator specific to subpopulations within the immune microenvironment, connecting immune remodeling to both inflammatory and proliferative chondrocytes in OA. Considering the diversity of chondrocytes, the presence of immune cells, and catabolic processes, our results emphasize the significance of CORO1A as a mechanistic factor contributing to cartilage degradation, suggesting its potential as a therapeutic target for OA.
Introduction:
Osteoarthritis (OA) is increasingly understood as a condition influenced by the diversity of chondrocytes and immune system dysfunction; however, the specific molecular elements connecting distinct chondrocyte populations to the immune environment remain inadequately explored. The protein CORO1A, associated with the cytoskeleton and implicated in immune regulation, has not been thoroughly investigated in the context of OA or through single-cell analysis.
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