Bone has the capacity for repair and regeneration. The repair process is thought to be locally regulated by growth factors. One of the growth factors that potentially plays a significant role in these processes is platelet-derived growth factor (PDGF). Two different PDGF genes have been identified, PDGF-A and PDGF-B, whose gene products give rise to biologically active dimers. We now report that PDGF-AA and PDGF-BB exhibit saturable binding to normal human osteoblastic cells. By Scatchard analysis we estimate that there are approximately 43,000 PDGF-AA binding sites per cell, with a dissociation constant (Kd) of 2.2 x 10(-10)M, and 55,000 high-affinity PDGF-BB binding sites per cell, with a Kd of 1.2 x 10(-10)M. The functional consequence of PDGF binding was also assessed. PDGF-AA and PDGF-BB both stimulated migration of normal human osteoblastic cells and stimulated thymidine incorporation. To gain insight into potential transmodulation of the PDGF response, we investigated the capacity of interleukin-1 beta (IL-1 beta), a cytokine that induces bone resorption, to modulate PDGF binding and PDGF-induced biological activity. IL-1 beta significantly reduced PDGF-AA binding and significantly decreased both PDGF-AA-mediated cell migration and thymidine incorporation. In contrast, IL-1 beta had only a small effect of PDGF-BB binding and PDGF-BB-induced biological activity in normal human osteoblastic cells.

This paper describes a quantitative study of periodontal defects produced in a skull model using subtraction images obtained with a digital imaging device, radiovisiography (RVG). Analysis using radiovisiography was compared to changes in weight and volume determined by physical measurements. Four types of periodontal defects were studied: 2-wall, 3-wall, crater, and furcation. All defects were fabricated on posterior teeth in alveolar bone and done with triplicate samples. Defects were made progressively larger in approximately 1 mm steps allowing examination of defects ranging from 1 mm to 5 mm. Radiographic images before and after each step were obtained with a radiovisiography system and subtracted. Changes in weight and defect volume were also recorded and compared to the results obtained after each step from the digital subtraction. For each defect type, a regression analysis was performed to compare changes in bone mass determined by weight with calculated bone loss determined by subtraction radiography or by volume measurements. When the calculated bone losses were compared to the true bone losses it was evident that the subtraction method frequently, but not always, underestimated the lesion sizes. For all lesions the average underestimation was 22%. The largest underestimation occurred with furcation lesions where the measured bone loss was underestimated on average by 67%. Two-walled lesions were underestimated by 30%, 3-wall lesions by 3%, and crater lesions were overestimated by 10%. Furthermore, the accuracy of each 1 mm step in bone loss varied considerably. At present, the imaging system is not sufficiently accurate to establish absolute determinations of the bone loss, but would be clinically useful in determining relative changes in bone loss or gain after treatment. In addition, caution must be taken in interpreting a given change in calculated bone loss, since considerable variation may result in either underestimation or overestimation of bone loss.

Platelet-derived growth factor (PDGF) is thought to play a significant role in bone repair and regeneration. We previously demonstrated that PDGF-AA-induced chemotaxis and proliferation can be modulated by IL-1. We now report that IL-1 and transforming growth factor-beta (TGF-beta) significantly decrease the number of PDGF-AA binding sites in both normal and tumor-derived human osteoblastic cells, whereas PDGF-BB binding is minimally affected. The affinity of PDGF-AA binding remains unchanged in the presence of IL-1, but is slightly reduced by TGF-beta as demonstrated by Scatchard analysis. We also showed that tyrosyl kinase phosphorylation after PDGF-AA binding is decreased in the presence of both IL-1 and TGF-beta. Northern blot analysis indicates that both IL-1 and TGF-beta decrease the expression of PDGF-alpha receptor mRNA. These results suggest that IL-1 and TGF-beta have the potential to regulate PDGF-AA-induced biologic activity in normal human osteoblastic cells and in human osteoblastic sarcoma cells by decreasing the levels of the PDGF-alpha receptor.