Intrinsic Bone Defects in Cystinotic Mice

The American Journal of Pathology
Giulia BattafaranoAndrea Del Fattore

Abstract

Cystinosis is a rare lysosomal storage disorder caused by loss-of-function mutations of the CTNS gene, encoding cystinosin, a symporter that mediates cystine efflux from lysosomes. Approximately 95% of patients with cystinosis display renal Fanconi syndrome, short stature, osteopenia, and rickets. In this study, we investigated whether the absence of cystinosin primarily affects bone remodeling activity, apart from the influences of the Fanconi syndrome on bone mineral metabolism. Using micro-computed tomography and histomorphometric and bone serum biomarker analysis, we evaluated the bone phenotype of 1-month-old Ctns-/- (KO) male mice without tubulopathy. An in vitro study was performed to characterize the effects of cystinosin deficiency on osteoblasts and osteoclasts. Micro-computed tomography analysis showed a reduction of trabecular bone volume, bone mineral density, and number and thickness in KO mice compared with wild-type animals; histomorphometric analysis revealed a reduction of osteoblast and osteoclast parameters in tibias of cystinotic mice. Decreased levels of serum procollagen type 1 amino-terminal propeptide and tartrate-resistant acid phosphatase in KO mice confirmed reduced bone remodeling activity. In vitro...Continue Reading

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Citations

Jun 10, 2019·Journal of Inherited Metabolic Disease·Katharina HohenfellnerDieter Haffner
May 2, 2020·International Journal of Molecular Sciences·Irma Machuca-GayetJustine Bacchetta
May 16, 2020·The Journal of Clinical Endocrinology and Metabolism·Annika EwertDieter Haffner

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