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Göteborg Pediatric Growth Research Center (R.B., B.A., H.S.K., D.S.-E., R.W., B.K., K.A.-W.), Department of Pediatrics, The Institute of the Health of Women and Children, 416 85 Göteborg, Sweden; RCEM (B.A., B.O., B.C., L.M.S.C.), Department of Internal Medicine, The Sahlgrenska Academy at Göteborg University, 413 45 Göteborg, Sweden; Department of Pediatrics (R.B.), Landspitali University Hospital, 101 Reykjavik, Iceland; and Department of Pediatrics (H.S.K.), Daini Hospital, Tokyo Womens Medical University, 116-8567 Tokyo, Japan
Address all correspondence and requests for reprints to: Ragnar Bjarnason, The Sahlgrenska Academy at Göteborg University, Department of Pediatrics, Göteborg Pediatric Growth Research Center, The Queen Silvia Childrens Hospital, S-416 85 Göteborg, Sweden. E-mail: ragnar.bjarnason{at}vgregion.se.
Both GH and IGF-I stimulate bone growth, but the molecular mechanisms mediating their effects on the growth plate are not fully understood. We measured gene expression by microarray analysis in primary cultured human chondrocytes treated with either GH or IGF-I. One of the genes found to be up-regulated by both GH and IGF-I was that encoding cartilage oligomeric matrix protein (COMP). This protein is predominantly found in the extracellular matrix of cartilage. Mutations in the COMP gene have been associated with syndromes of short stature. To verify that COMP is regulated by GH in vivo, we measured COMP levels in serum in short children treated with GH. The study included 113 short prepubertal children (14 girls and 99 boys) with a mean (± SD) age of 8.84 ± 2.76 yr, height SD score of 2.74 ± 0.67, and IGF-I SD score of 1.21 ± 1.07 at the start of GH administration. Serum levels of COMP were 1.58 ± 0.28, 1.83 ± 0.28 (P < 0.0001), 1.91 ± 0.28 (P < 0.0001), 1.78 ± 0.28 (P < 0.001), and 1.70 ± 0.24 (P < 0.05) µg/ml at baseline and after 1 wk and 1, 3, and 12 months, respectively.
In conclusion, we have demonstrated that COMP expression is up-regulated by both GH and IGF-I in primary cultured human chondrocytes. Furthermore, serum levels of COMP increase after the start of GH treatment in short children.
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