Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice

Mark O.R. Hajjawi, Vicky E. MacRae, Carmen Huesa, Alan Boyde, José Luis Millán, Timothy R. Arnett, Isabel R. Orriss

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)139-147
Number of pages9
JournalBone
Volume69
DOIs
Publication statusPublished - 28 Sep 2014
Externally publishedYes

Fingerprint

Osteocytes
Collagen
Osteoclasts
nucleotide pyrophosphatase
Ear Auricle
Nucleotides
Bone and Bones
Vibrissae
X-Ray Microtomography
Porosity
Humerus
Phosphoric Diester Hydrolases
Trachea
Electron Scanning Microscopy
Blood Vessels
Cortical Bone
Spine
Joints
Bone Marrow

Keywords

  • NPP1
  • Osteocytes
  • Osteoclasts
  • Soft tissue mineralisation
  • Pyrophosphate

Cite this

Hajjawi, M. O. R., MacRae, V. E., Huesa, C., Boyde, A., Millán, J. L., Arnett, T. R., & Orriss, I. R. (2014). Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice. Bone, 69, 139-147. https://doi.org/10.1016/j.bone.2014.09.016
Hajjawi, Mark O.R. ; MacRae, Vicky E. ; Huesa, Carmen ; Boyde, Alan ; Millán, José Luis ; Arnett, Timothy R. ; Orriss, Isabel R. / Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice. In: Bone. 2014 ; Vol. 69. pp. 139-147.
@article{42b0d61cab3d47e69aa9ad1d32ddb0e1,
title = "Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice",
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.",
keywords = "NPP1, Osteocytes, Osteoclasts, Soft tissue mineralisation, Pyrophosphate",
author = "Hajjawi, {Mark O.R.} and MacRae, {Vicky E.} and Carmen Huesa and Alan Boyde and Mill{\'a}n, {Jos{\'e} Luis} and Arnett, {Timothy R.} and Orriss, {Isabel R.}",
note = "Copyright {\circledC} 2014. Published by Elsevier Inc.",
year = "2014",
month = "9",
day = "28",
doi = "10.1016/j.bone.2014.09.016",
language = "English",
volume = "69",
pages = "139--147",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier B.V.",

}

Hajjawi, MOR, MacRae, VE, Huesa, C, Boyde, A, Millán, JL, Arnett, TR & Orriss, IR 2014, 'Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice' Bone, vol. 69, pp. 139-147. https://doi.org/10.1016/j.bone.2014.09.016

Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice. / Hajjawi, Mark O.R.; MacRae, Vicky E.; Huesa, Carmen; Boyde, Alan; Millán, José Luis; Arnett, Timothy R.; Orriss, Isabel R.

In: Bone, Vol. 69, 28.09.2014, p. 139-147.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice

AU - Hajjawi, Mark O.R.

AU - MacRae, Vicky E.

AU - Huesa, Carmen

AU - Boyde, Alan

AU - Millán, José Luis

AU - Arnett, Timothy R.

AU - Orriss, Isabel R.

N1 - Copyright © 2014. Published by Elsevier Inc.

PY - 2014/9/28

Y1 - 2014/9/28

N2 - 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.

AB - 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.

KW - NPP1

KW - Osteocytes

KW - Osteoclasts

KW - Soft tissue mineralisation

KW - Pyrophosphate

U2 - 10.1016/j.bone.2014.09.016

DO - 10.1016/j.bone.2014.09.016

M3 - Article

VL - 69

SP - 139

EP - 147

JO - Bone

JF - Bone

SN - 8756-3282

ER -

Hajjawi MOR, MacRae VE, Huesa C, Boyde A, Millán JL, Arnett TR et al. Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice. Bone. 2014 Sep 28;69:139-147. https://doi.org/10.1016/j.bone.2014.09.016