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Cell Signalling

Intracellular cascades, including the RhoA/ROCK and p38 pathways, that convert stimuli into chondrocyte responses.

Cell signalling is the set of intracellular cascades that convert external stimuli into the gene-expression and cytoskeletal changes that determine chondrocyte behaviour [1]. A central axis is RhoA/ROCK, which drives actin polymerisation and stress-fibre formation and, through them, controls the activity of the master chondrogenic factor SOX9 [1]. Running in parallel, the p38 mitogen-activated protein kinase pathway is activated in stressed chondrocytes and promotes senescence and dedifferentiation [2]. Inflammatory input converges on nuclear factor kappa B, which switches on catabolic genes and matrix-degrading enzymes while repressing chondrogenic programmes [3].

These pathways do not act in isolation; mechanical, inflammatory and metabolic signals are integrated so that the balance of their outputs sets the cell's fate [3]. Because the same signalling nodes both maintain and, when dysregulated, undermine the chondrocyte phenotype, they are attractive points for therapeutic intervention [1]. Dissecting how the RhoA/ROCK and p38 cascades reshape the chondrocyte is the mechanistic heart of Jessica's thesis [2].

References

  1. [1] J. C. Lauer, M. Selig, M. L. Hart, B. Kurz, and B. Rolauffs, "Articular chondrocyte phenotype regulation through the cytoskeleton and the signaling processes that originate from or converge on the cytoskeleton," Int. J. Mol. Sci., vol. 22, no. 6, art. no. 3279, 2021.
  2. [2] S. Ashraf, B.-H. Cha, J.-S. Kim, J. Ahn, I. Han, H. Park, and S.-H. Lee, "Regulation of senescence associated signaling mechanisms in chondrocytes for cartilage tissue regeneration," Osteoarthritis Cartilage, vol. 24, no. 2, pp. 196–205, 2016.
  3. [3] E. Horváth, Á. Sólyom, J. Székely, E. E. Nagy, and H. Popoviciu, "Inflammatory and metabolic signaling interfaces of the hypertrophic and senescent chondrocyte phenotypes associated with osteoarthritis," Int. J. Mol. Sci., vol. 24, no. 22, art. no. 16468, 2023.