Development of the bones and synovial joints in the rat model of the VATER association.

The adriamycin-induced rat model of the Vertebral, Anorectal, Tracheo-Esophageal, Radial and Renal (VATER) association produces a variety of vertebral, rib, and limb abnormalities. This study was designed to document accurately the nature of these abnormalities and to determine whether synovial joints are affected. Fetuses from pregnant Sprague Dawley rats that had received intraperitoneal injections of 1.75 mg/kg of adriamycin on days 6-9 or 10-13 of gestation were harvested. Double-stained skeletal preparations and histological sections were examined for vertebral, rib, and limb anomalies. The incidence of anomalies was high in the group treated on gestational days (GD) 6-9, while it was low in the GD 10-13 group. The length and thickness of the long bones were reduced, with bowing and reduction in their endochondral ossification. Sirenomelia occurred in the group treated on GD 6-9, and was often associated with a short tail and anal atresia. The joint cavities, and intra-articular structures such as menisci and the cruciate ligaments developed normally from the mesenchymal interzone. These data indicate that adriamycin inhibits skeletal growth and differentiation without any interference in the differentiation of the mesenchymal interzone, thus producing normal synovial joints.

Cell death in the developing chick knee joint: I. Spatial and temporal patterns.

The occurrence, distribution and nature of cell death has been studied in the interzone of the developing knee joint of the chick by optical, transmission and scanning electron microscopy. Cell death precedes and accompanies the process of formation of the joint cavity (apart from the femoropatellar component), and is also associated with the surfaces of intra-articular structures as they differentiate within the interzone. Cell death in the knee joint shows many of the morphological characteristics of apoptosis. It is proposed that cell death is one factor in the process of cavity formation in the joint.

Retinoic acid-induced abnormal development of hindlimb joints in the mouse.

Following a single oral dose of 200 mg/kg of retinoic acid (RA) to pregnant TO mice on day 12 of gestation, fetuses were collected on day 18. RA-treatment resulted in a modest increase in embryo resorption, a significant reduction in fetal body weight and a 96% incidence of limb malformations. Both fore- and hindlimbs were malformed in equal frequency. In this study, only the anomalies of the hindlimbs have been considered. Alizarin stained skeletal preparations revealed a reduction in both length and thickness as well as bowing of the long bones. Agenesis of most of the metatarsals and some toes and/or phalanges was also noted. Paraffin sections cut serially confirmed the gross observations. Additionally, the joint cavities were found to be absent and the cartilaginous ends of the articulating bones were continuous with each other. In some this union was partial and occasionally the joint was only represented by a fine slit. The synovial membrane and other intra-articular structures were either rudimentary or absent. There was a marked reduction in endochondral ossification. Bony union in syndactyly was occasionally observed. These data indicate that a high dose of RA, both inhibits skeletal growth and interferes with the differentiation of the inter-zone mesenchyme, thus resulting in abnormalities of the joints in the TO mouse fetuses.