PROLIFERATION AND COLLAGEN BIOSYNTHESIS OF OSTEOBLASTS AND CHONDROCYTES IN SHORT RIB SYNDROME TYPE BEEMER

We report on a case of lethal short-limbed skeletal dysplasia with ext remely short ribs, median cleft upper lip and palate, malrotation of i ntestine, lung hypoplasia with bilateral segmentation defect, atrial s eptum defect, union of distal urethra and vagina, and complex brain ma lformations. Based on radiological criteria and the pattern of associa ted abnormalities a short rib syndrome without polydactyly (Type Beeme r) was diagnosed. Morphologically, the growth plate showed a reduced p roliferation zone and an enlarged zone of hypertrophic cartilage. In a ddition, islands of persistent hypertrophic cartilage were present eve n in the metaphysis. In monolayer cell cultures supplemented with 10% fetal calf serum proliferation was normal in articular chondrocytes, r educed in costal chondrocytes, and elevated in osteoblasts from the pa tient. Clonal growth of costal and articular chondrocytes in methylcel lulose could be stimulated normally by insulin-like growth factor-I (I GF-I), IGF-II, and human growth hormone (hGH). However, the response t o transforming growth factor beta1 (TGF-beta1) was markedly elevated i n articular chondrocytes of the patient compared to those of 3 fetal c ontrols. Quantitative collagen synthesis in both osteoblasts and chond rocytes from the patient did not differ significantly from that of con trols. Osteoblasts synthesized predominantly collagen I and minor amou nts of collagen III, chondrocytes synthesized primarily collagen II. A ll collagen chains including CNBr-peptides of collagen II showed norma l migration in PAA gel electrophoresis.