Progression of vertebral bone disease in mucopolysaccharidosis VII dogs from birth to skeletal maturity

Copyright © 2021 Elsevier Inc. All rights reserved..

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, leading to accumulation of incompletely degraded heparan, dermatan and chondroitin sulfate glycosaminoglycans. Patients with MPS VII exhibit progressive spinal deformity, which decreases quality of life. Previously, we demonstrated that MPS VII dogs exhibit impaired initiation of secondary ossification in the vertebrae and long bones. The objective of this study was to build on these findings and comprehensively characterize how vertebral bone disease manifests progressively in MPS VII dogs throughout postnatal growth. Vertebrae were collected postmortem from MPS VII and healthy control dogs at seven ages ranging from 9 to 365 days. Microcomputed tomography and histology were used to characterize bone properties in primary and secondary ossification centers. Serum was analyzed for bone turnover biomarkers. Results demonstrated that not only was secondary ossification delayed in MPS VII vertebrae, but that it progressed aberrantly and was markedly diminished even at 365 days-of-age. Within primary ossification centers, bone volume fraction and bone mineral density were significantly lower in MPS VII at 180 and 365 days-of-age. MPS VII growth plates exhibited significantly lower proliferative and hypertrophic zone cellularity at 90 days-of-age, while serum bone-specific alkaline phosphatase (BAP) was significantly lower in MPS VII dogs at 180 days-of-age. Overall, these findings establish that vertebral bone formation is significantly diminished in MPS VII dogs in both primary and secondary ossification centers during postnatal growth.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:133

Enthalten in:

Molecular genetics and metabolism - 133(2021), 4 vom: 18. Aug., Seite 378-385

Sprache:

Englisch

Beteiligte Personen:

Peck, Sun H [VerfasserIn]
Lau, Yian Khai [VerfasserIn]
Kang, Jennifer L [VerfasserIn]
Lin, Megan [VerfasserIn]
Arginteanu, Toren [VerfasserIn]
Matalon, Dena R [VerfasserIn]
Bendigo, Justin R [VerfasserIn]
O'Donnell, Patricia [VerfasserIn]
Haskins, Mark E [VerfasserIn]
Casal, Margret L [VerfasserIn]
Smith, Lachlan J [VerfasserIn]

Links:

Volltext

Themen:

Biomarker
Canine
Growth plate
Journal Article
Lysosomal storage disease
Mucopolysaccharidosis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Spine

Anmerkungen:

Date Completed 06.01.2022

Date Revised 02.08.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ymgme.2021.06.005

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM327023309