Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1−/− mice

Hajjawi, M. O.R., MacRae, V. E., Huesa, C., Boyde, A., Millán, J. L., Arnett, T. R. and Orriss, I. R. (2014) Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1−/− mice. Bone, 69, pp. 139-147. (doi: 10.1016/j.bone.2014.09.016) (PMID:25260930) (PMCID:PMC4228085)

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Abstract

Ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) hydrolyse nucleotide triphosphates to the corresponding nucleotide monophosphates and the mineralisation inhibitor, pyrophosphate (PPi). This study examined the role of NPP1 in osteocytes, osteoclasts and cortical bone, using a mouse model lacking NPP1 (Enpp1−/−). We used microcomputed tomography (μCT) to investigate how NPP1 deletion affects cortical bone structure; excised humerus bones from 8, 15 and 22-week old mice were scanned at 0.9 μm. Although no changes were evident in the cortical bone of 8-week old Enpp1−/− mice, significant differences were observed in older animals. Cortical bone volume was decreased 28% in 22-week Enpp1−/− mice, whilst cortical porosity was reduced 30% and 60% at 15 and 22-weeks, respectively. This was accompanied by up to a 15% decrease in closed pore diameter and a 55% reduction in the number of pores. Cortical thickness was reduced up to 35% in 15 and 22-week Enpp1−/− animals and the endosteal diameter was increased up to 23%. Thus, the cortical bone from Enpp1−/− mice was thinner and less porous, with a larger marrow space. Scanning electron microscopy (SEM) revealed a decrease in the size and number of blood vessel channels in the cortical bone as well as a 40% reduction in the mean plan area of osteocyte lacunae. We noted that the number of viable osteocytes isolated from the long bones of Enpp1−/− mice was decreased ≤ 50%. In contrast, osteoclast formation and resorptive activity were unaffected by NPP1 deletion. μCT and histological analysis of Enpp1−/− mice also revealed calcification of the joints and vertebrae as well as soft tissues including the whisker follicles, ear pinna and trachea. This calcification worsened as the animals aged. Together, these data highlight the key role of NPP1 in regulating calcification of both soft and skeletal tissues.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Huesa, Dr Carmen
Authors: Hajjawi, M. O.R., MacRae, V. E., Huesa, C., Boyde, A., Millán, J. L., Arnett, T. R., and Orriss, I. R.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Bone
Publisher:Elsevier
ISSN:8756-3282
ISSN (Online):1873-2763
Published Online:28 September 2014
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Bone 69:139-147
Publisher Policy:Reproduced under a Creative Commons Licence

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