Bone Abstracts

Background: Proline and hydroxyproline account for ~25% of aminoacids in collagen., Prolidase (peptidase D (EC 3.4.14.9)), cleaves iminodipeptides with a C-terminal proline or hydroxyproline, playing a major role in collagen catabolism. Mice with prolidase deficiency (PD) present with varied phenotypes including reduced size compared to wild-type littermates. We measured structural and mechanical properties of bones in PD mice.

Methods: Whole femurs from 28-day-old male (n=6) and female (n=10) mice with PD (HOMO) and wild-type mice (WT: male, n=6; female, n=10) and male 2 month old mice (HOMO: n=6, WT: n=6) were scanned on a Skyscan μ-CT 1172 using published protocols. Bone mineral density was calculated by linear extrapolation using a 2 mm phantom rod pair containing 0.25 and 0.75 g/cm³ calcium hydroxyapatite. Data were analysed by two-way ANOVA with Tukey post-hoc analysis for genotype and gender effects. Mechanical properties of whole femurs were analysed using microindentation (Biodent).

Results: PD resulted in significant reductions in trabecular bone volume (P<0.0001), trabecular number (P<0.0001), trabecular thickness (P=0.018), cortical bone volume (P=0.004) in 28-day-old mice only and femoral length at 28 days (P=0.0005) and 2 months (P=0.017). There was no effect of genotype on mechanical properties.

Conclusions: PD in mice reduced trabecular bone volume, thickness and number as well as cortical bone volume and femoral length in comparison to wild-type mice at 28 days. This indicates that delayed collagen recycling through PD affected bone structure at early stages of development. The catch up seen by 2 months potentially reflects reduced need for rapid collagen turnover. There was no clear effect of PD on bone material properties measured by microindentation. The prolidase deficiency phenotype is essentially osteoporotic in early life.