S100A1 and S100B: Calcium Sensors at the Cross‐Roads of Multiple Chondrogenic Pathways

The S100 protein family comprises more than 20 members of small calcium binding proteins operating as Ca2 +-activated switches that interact and modulate the activity of a large number of targets. S100A1 and S100B, two members of this family, have been recently associated with the differentiation status of human articular chondrocytes. Both proteins are homogeneously expressed in all cartilage zones, their expression decreases during chondrocyte dedifferentiation, and can be induced under conditions promoting redifferentiation. Although S100 proteins have a broad range of extra- and intracellular roles, functional studies of S100 proteins expressed in chondrocytes have focused on their extracellular roles linked to catabolic processes. The intracellular roles of S100A1 and S100B in chondrocytes remain largely unexplored, yet the few studies addressing their intracellular activity point toward potentially important functions in chondrocyte biology. This review summarizes reported intracellular S100A1 and S100B regulatory functions described in other cell types that could be also involved in the regulation of chondrogenic processes in cartilage. Potential roles of S100A1 and S100B in the TGF-β-SMAD, the cAMP-PKA-CREB, and the PI3K-AKT pathways, Ca2+ homeostasis, cytoskeleton dynamics, the calcineurin-NFAT pathway, interactions with the p53 family, and the Hippo pathway are examined in the context of chondrocyte biology. Based on the plethora of interactions of S100A1 and S100B with different molecular partners playing essential roles in chondrocyte biology, and the staggering complexity and ubiquity of cross-talk among these partners, we hypothesize that these S100 proteins play fundamental roles in the spatial and temporal regulation of chondrogenesis. J. Cell. Physiol. 232: 1979-1987, 2017. © 2016 Wiley Periodicals, Inc.