gms | German Medical Science

Objectives: It is well known that processes revolving the bone can vary between sexes whereas females generally show weaker bones. We have previously shown that the heparan sulfate proteoglycan Syndecan-1 plays a vital role in osteogenesis and bone cell crosstalks as it takes part in osteoclast activation and angiogenesis. In the current project we compared bone structure in the trabecular region of mice lacking Syndecan-1 to wild type in male and female mice. We hypothesized that any differences might be caused by an alteration in vascularization, therefore we also compared angiogenesis at the growth plate. Our general aim is to better understand the role of Syndecan-1 in osteogenesis and fracture and translate this knowledge into clinical use.

Methods: Left femora of four months old C57BL/6 mice (11 wildtype: 5 female, 6 male & 14 Sdc1-/-: 9 female, 5 male) were analyzed using microCT to evaluate bone specific parameters including cortical thickness, cortical & trabecular mineral density, bone volume/tissue volume (BV/TV), trabecular thickness, number and separation. Results were evaluated with GraphPad Prism (Two-way ANOVA, p<0.05). Furthermore, tissue slices (5µm, 80µm) were created using a cryotome. Blood vessels were stained for fluorescence microscopy using endomucin antibody. Vessel bulbs at the chondro-osseous border at the growth plate were quantified using a custom made semi-quantitative method.

Results and conclusion: Analysis of microCT pictures showed no significant differences in any parameter for female Sdc1-/- mice. The male Sdc1-/- group showed significantly reduced BV/TV, trabecular number and cortical and trabecular mineral density compared to male wildtype mice. Comparing genotype-matched groups also confirmed previous findings of stronger bones in male mice, validating our method. The endomucin staining revealed significant reduction in neoangiogenesis at the chondro-osseous border for Sdc1-/- mice of both sexes.

Syndecan-1 deficiency has a strong impact on bone in males with a weakening of the trabecular structure, but not in female mice although neoangiogenesis at the chondro-osseous border is reduced in both sexes. Since vascularization does not seem to differ between sexes, it is unlikely to be the reason for the increased bone loss in male Sdc1-/- mice. It is possible that a reduced osteoclast activation leads to fewer osteoclasts and thus to the observed bone loss in Sdc1-/- mice.