Endocrine Abstracts

Introduction: SOCS2 is an important negative regulator of post-natal growth, as demonstrated by the SOCS2 null overgrowth phenotype. We have used SOCS2^−/− mice, alongside chondrocytes overexpressing SOCS2, to investigate the mode of action of SOCS2 at the epiphysis. SOCS2 maybe involved in growth retardation associated with chronic inflammatory disorders, therefore we studied LPS induced growth retardation in wild type (WT) and SOCS2^−/− mice.

Methods: Protein expression was determined by western blotting. SOCS1, 2 and 3 expression was analysed in response to GH (500 ng/ml) and IGF1 (50 ng/ml) in WT chondrocytes. WT and SOCS2^−/− murine primary chondrocytes were analysed for STAT activation in response to GH over time. Chondrogenic ATDC5 cells were used to overexpress SOCS2, and were also analysed for STAT phosphorylation.

To induce inflammation, 4-week-old WT and SOCS2^−/− mice were challenged daily with 50 μg/kg LPS (saline controls) for 7 days. Their body weights and tibia lengths were measured.

Results: SOCS2 expression increased in response to GH, but not IGF1. Neither SOCS1 nor 3 responded to GH or IGF1.

STATs1, 3 and 5 phosphorylation increased in response to GH, an effect that peaked after approximately 30 min and declined thereafter in WT chondrocytes and control ATDC5 cells. In SOCS2^−/− chondrocytes, STAT activation was increased and prolonged. No STAT activation by GH was observed in chondrocytes overexpressing SOCS2.

SOCS2^−/− mice were protected from LPS induced growth retardation, shown by significant increases in body weight and tibia length.

Conclusions: SOCS2 is the primary SOCS protein in the growth plate to respond to GH, were it is likely to inhibit chondrocyte STAT signalling in response to GH. Our preliminary data suggests that SOCS2^−/− mice are protected from LPS induced growth retardation. The role of SOCS2 in mediating the growth retardation observed during chronic inflammatory diseases warrants further investigation.