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

Abstract

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.

Fibroblast Growth Factor 9 (FGF9) negatively regulates the early stage of chondrogenic differentiation

“…Tyrosine kinase-mediated signaling modules that have been confirmed include phosphoinositide 3 kinase (PI3K), mitogen-activated protein kinase (MAPK), protein kinase C (PKC) as well as signal transcription and activation factor 1 (STAT1) [22]. The PI3K-AKT pathway is a signaling cascade functioning in both chondrogenesis of articular cartilage [24,25], which is essential for insulin-like growth factor I (IGF-1) induced differentiation of early chondrocytes from mesenchymal precursor cells [26]. AKT signaling can be activated in resting and proliferating chondrocytes [15].…”

S100A1 is a Potential Biomarker for Papillary Thyroid Carcinoma Diagnosis and Prognosis

“…Similar to most S100 family proteins, conformational changes take place in S100A1 upon binding calcium and interacting with many target proteins 8 . Through specific interactions, S100A1 is involved in many pathophysiological processes such as synapse release 36 , cytoskeletal proteins dynamics 32 , and regulation of transcription factors 37 . S100A1 was also reported to be involved in the occurrence and progression of tumors.…”

Rho-kinase inhibitor Y-27632 and hypoxia synergistically enhance chondrocytic phenotype and modify S100 protein profiles in human chondrosarcoma cells

“…Possible mechanism for S100 protein actions may involve TGF-β/SMAD, cyclic AMP (cAMP)/protein kinase A (PKA)/cAMP response element binding protein (CREB), phosphoinositide-3 kinase (PI3K)/Akt, Ca 2+ homeostasis, calcineurin/NFAT and RAGE related pathways, as reviewed recently 43 . TGF-β is known to stimulate the early events in chondrogenesis and inhibit terminal hypertrophic chondrocyte differentiation, and S100-A1 and S100-B may modulate this signaling via the interactions of PP5-TRP 30 .…”