ABSTRACT
Growth plate is an avascular tissue, which has been reported to be capable of retarding tumor spread. It is believed that angiogenic inhibitor(s) exist to inhibit the neo-vascularization of tumor, thus impeding the tumor growth. In this study, growth plate chondrocyte-derived TGFbeta1 was identified to be anti-angiogenic. It was found that growth plate chondrocytes (GPC) secreted TGFbeta1 mostly in latent form as demonstrated by gel filtration and immunoblotting. Enzyme-linked immunosorbent assay (ELISA) was followed to quantify TGFbeta1 in GPC conditioned medium (CM), in which 866 pg/ml of TGFbeta1 was found. Besides, the angiogenesis inhibitory effect of GPC CM was abolished by the addition of anti-TGFbeta1 antibody in the in vitro culture system and the in vivo chick chorioallantoic membrane (CAM) assay. This confirmed the anti-angiogenic properties of chondrocyte-derived TGFbeta1. TGFbeta1 was expressed predominantly in the proliferative zone of porcine growth plate. This explains the low incidence of tumor invasion across the entire growth plate. Also, this helps to explain the observation that tumor invasion across the physis increases with age as the proliferative zone gradually disappears. J. Cell. Biochem. Suppl. 36: 79-88, 2001.
Subject(s)
Angiogenesis Inhibitors/metabolism , Chondrocytes/metabolism , Transforming Growth Factor beta/metabolism , Allantois/blood supply , Animals , Antibodies , Blotting, Western , Cell Division , Cell Line , Chick Embryo , Chondrocytes/cytology , Chorion/blood supply , Chromatography, Gel , Electrophoresis, Polyacrylamide Gel , Growth Plate/cytology , Growth Plate/metabolism , Humans , Immunohistochemistry , Swine , Transforming Growth Factor beta/immunology , Transforming Growth Factor beta1ABSTRACT
A large osteopenic animal model that resembles human osteoporotic changes is essential for osteoporosis research. This study aimed at establishing a large osteopenic animal model in goats. Twenty-five Chinese mountain goats were used in which they were either ovariectomized (OVX) and fed with a low-calcium diet (n = 16) or sham-operated (SHAM; n = 9). Monthly photodensitometric analysis on proximal tibial metaphysis and calcaneus was performed. Two iliac crest biopsy specimens obtained before and 6 months after OVX were used for bone mineral density (BMD) measurement with peripheral quantitative computed tomography (pQCT). Lumbar vertebrae (L2 and L7), humeral heads, and calcanei were collected for BMD measurement after euthanasia. The humeral heads and calcanei were used in biomechanical indentation test. BMD measurement showed a significant 25.0% (p = 0.006) decrease in BMD of the iliac crest biopsy specimens 6 months after OVX. It also was statistically significant when compared with the SHAM (p = 0.028). BMD at L2, L7, calcaneus, and humeral head reduced by 24-33% (p ranged from 0.001 to 0.011) when compared with the SHAM. Photodensitometry showed a continuous decrease in bone density after OVX. There were significant decreases of 18.9% in proximal tibial metaphysis (p = 0.003) and 21.8% in calcaneus (p = 0.023) in the OVX group 6 months postoperatively. Indentation test on the humeral head and calcaneus showed a significant decrease 52% (p = 0.006) and 54% (p = 0.001), respectively, in energy required for displacement of 3 mm in the OVX group compared with the SHAM group. The decreases correlated significantly to the decrease in BMD of the corresponding specimens (r2 = 0.439 and 0.581; p < 0.001 for both). In conclusion, this study showed that OVX plus a low-calcium diet could induce significant osteopenia and deterioration of mechanical properties of the cancellous bone in goats.