http://www.biosciproceedingsandabstracts.com/

ISSN 2052-1219 (online)

Bone Abstracts (2013) 2 OC22 | DOI: 10.1530/boneabs.2.OC22

Prolidase deficient mice are osteoporotic in early life

Sarah Foster1,*, Peter Grabowski3, Orla Gallagher1, Roberta Besio3, Antonio Rossi3, Nick Bishop1,2 & Antonella Forlino3


1Department of Human Metabolism, University of Sheffield, Sheffield, UK; 2Sheffield Children’s Hospital, Sheffield, UK; 3Department of Molecular Medicine, University of Pavia, Pavia, Italy; 4Department of Oncology, University of Sheffield, Sheffield, UK. *Winner of New Investigator Award


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.

1 month old miceHOMOWT
BV/TVMeanS.E.M.nMeanS.E.M.n
Female5.950.719*10.200.7210
Male7.051.06615.481.636
Tb.Th
Female0.0330.00069*0.0340.000710
Male0.0330.000960.0350.00046
Tb.N
Female1.6900.1659*2.1090.21210
Male2.1490.31564.4330.4356
Femur length
Female10.3240.07869*10.9850.16539*
Male9.9600.4999611.4200.34356
Ct.BV
Female0.3590.004100.3880.01510
Male0.1100.00760.1210.0046
2 month
Femur length
Male13.660670.255952614.492170.1410966

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.

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