Effects of Bone CS-Proteoglycans, DS-Decorin, and DS-Biglycan on Hydroxyapatite Formation in a Gelatin Gel

Abstract

The small leucine-rich bone proteoglycans, biglycan and decorin, can be purified by chromatography on hydroxyapatite columns, demonstrating their potential affinities for bone apatite. To determine their effects on in vitro apatite formation and growth, a mixture of the chondroitin-sulfate (CS) bone proteoglycans, or purified fractions of the dermatan sulfate (DS) containing proteoglycans, DS-decorin and DS-biglycan obtained from skin and articular cartilage, respectively, were analyzed in a gelatin gel diffusion system in which apatite formation occurs in the absence of proteins in a 3.5 day period. Low concentrations of the bone CS-proteoglycan mixture and low DS-biglycan concentrations (5-25 microg/ml) increased apatite formation relative to proteoglycan-free controls at 3.5 days. The CS-proteoglycan mixture was less effective at 50 microg/ml than at 10 microg/ml. DS-biglycan was similarly most effective at 5-25 microg/ml. At 5 days, when apatite growth and proliferation were assessed, 10 and 50 microg/ml of both CS-bone proteoglycan and DS-biglycan increased mineral yields. DS-decorin, in contrast, had no significant effect on mineral accumulation at any of these concentrations. In seeded growth experiments, 1 and 10 microg/ml CS-proteoglycan and 10 and 50 microg/ml DS-biglycan were significant effective inhibitors of mineral accretion, whereas DS-decorin showed no tendency to inhibit seeded growth. Using molar extinction coefficients to determine concentrations, the binding of DS-biglycan and DS-decorin to apatite (specific surface 54 m2/g) was determined using a Langmuir adsorption isotherm model. DS-biglycan had a greater affinity for apatite than DS-decorin (0.285 ml/micromol versus 0.0098 ml/micromol). DS-biglycan binding was more specific with fewer binding sites (3.5 micromol/m2 compared with 18. 2 micromol/m2 for DS-decorin). Data suggest that of the small proteoglycans, biglycan may play a more significant role than decorin in the regulation of mineralization.

Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly Zoledronic acid

“…Moreover, because of the anatomic area selection criteria employed in this study, these differences are not attributable to the antiresorptive effect of ZOL. To further explore this finding, it was decided to monitor the relative GAG (indicative of proteoglycans) content in the two groups because in vitro studies had reported previously that lower proteoglycan concentrations increase the formation of hydroxyapatite crystals to a greater extent than higher ones, (25) and it also has been suggested that the small cellular/pericellular matrix proteoglycan decorin may act as an inhibitor of collagen matrix mineralization, thus modulating the timing of matrix mineralization. (26) Of course, it should be kept in mind that these studies involved solution and cell culture studies, so how these findings extrapolate to bone tissue is uncertain.…”

Biomimetic Extracellular Matrix-Incorporated Scaffold Induces Osteogenic Gene Expression in Human Marrow Stromal Cells

“…Published reports indicate that biglycan may modulate osteoblast differentiation 44 and may also be involved in the nucleation of hydroxyapatite. 45 COMP has been reported to be expressed by both embryonic and adult osteoblasts. 46 Immunostaining and in situ hybridization in published reports have shown the presence of COMP in the bone collar, the newly formed bone near the growth plate and in the diaphysis of a 21-day human fetus.…”

Distribution of biglycan and decorin in rat dental tissue

“…Their distribution and biological function vary significantly among tissues. Biglycan facilitates the initiation of apatite formation and inhibits its growth in a gelatin gel system (11). Previous results showed that this molecule has a role during the process of differentiation of odontoblasts and ameloblasts (12).…”