Endocrine Abstracts

The actions of SOCS2 on GH and IGF-1 signalling in growth plate chondrocytes have yet to be reported. During chronic paediatric inflammatory diseases retarded growth is seen in association with increased inflammatory cytokine levels, which is an effect that may involve SOCS2. The primary aim of this study was to investigate STAT signalling in chondrocytes in response to GH, IGF-1 and IL-1β. We also investigated the temporal expression of SOCS2 in response to GH and IGF-1 to examine which pathways are likely to regulate SOCS2.

STAT signalling in chondrocytes was investigated by Western Blotting using murine primary chondrocytes and the ATDC5 chondrogenic cell line. STAT1 and STAT3 phosphorylation increased in response to GH (500 ng/ml) in primary but not ATDC5 cells, a difference likely due to the fact ATDC5 cells are a transformed cells line. IL-1β increased STAT1 and STAT3 phosphorylation in both cells types. Phosphorylation of STAT5 increased significantly in ATDC5 and primary cells in response to GH, an effect that was inhibited by addition of IL-1β. No response to IGF-1 (50 ng/ml) was noted, which was expected as the IGF-1 receptor does not contain the specific tyrosine-based motifs recognized by STATs. In all cases total STAT1, 3 and 5 was unchanged.

The temporal expression of SOCS2 protein in response to GH and IGF-1 was also investigated in primary chondrocytes, at various time intervals (8, 24, 48 and 72 h). SOCS2 expression increased in response to GH, an effect that increased with time to peak after 48 h. SOCS2 expression was unaffected by IGF-1.

These data together confirm that GH signalling stimulates SOCS2 production, which is likely to act as a negative feedback loop to regulate STAT activation and GH signalling in chondrocytes. It is possible that IL-1β may increase SOCS2 expression, acting to inhibit GH signalling through STAT5.