Bone growth and turnover in progesterone receptor knockout mice

David J. Rickard, Urszula T. Iwaniec, Glenda Evans, Theresa E. Hefferan, Jamie C. Hunter, Katrina M. Waters, John P. Lydon, Bert W. O'Malley, Sundeep Khosla, Thomas C. Spelsberg, Russell T. Turner

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through thePRis necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain, and tibia longitudinal bone growth were normal in PRKO mice. In contrast, total, cancellous, and cortical bone mass were increased in the humerus of 12-wk-old PRKO mice, whereas cortical and cancellous bone mass in the tibia was normal. At 26 wk of age, cancellous bone area in the proximal tibia metaphysis of PRKO mice was 153% greater than age matched wild-type mice. The improved cancellous bone balance in 6-month-old PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice is not essential for bone growth and turnover. However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence.

Original languageEnglish (US)
Pages (from-to)2383-2390
Number of pages8
JournalEndocrinology
Volume149
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Bone Remodeling
Bone Development
Progesterone Receptors
Knockout Mice
Tibia
Weight Gain
X-Ray Microtomography
Humerus
Osteoclasts
Osteogenesis
Protein Isoforms
Body Weight
Cancellous Bone
Gene Expression
Bone and Bones
Mutation
Cortical Bone

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Rickard, D. J., Iwaniec, U. T., Evans, G., Hefferan, T. E., Hunter, J. C., Waters, K. M., ... Turner, R. T. (2008). Bone growth and turnover in progesterone receptor knockout mice. Endocrinology, 149(5), 2383-2390. https://doi.org/10.1210/en.2007-1247

Bone growth and turnover in progesterone receptor knockout mice. / Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jamie C.; Waters, Katrina M.; Lydon, John P.; O'Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

In: Endocrinology, Vol. 149, No. 5, 05.2008, p. 2383-2390.

Research output: Contribution to journalArticle

Rickard, DJ, Iwaniec, UT, Evans, G, Hefferan, TE, Hunter, JC, Waters, KM, Lydon, JP, O'Malley, BW, Khosla, S, Spelsberg, TC & Turner, RT 2008, 'Bone growth and turnover in progesterone receptor knockout mice', Endocrinology, vol. 149, no. 5, pp. 2383-2390. https://doi.org/10.1210/en.2007-1247
Rickard DJ, Iwaniec UT, Evans G, Hefferan TE, Hunter JC, Waters KM et al. Bone growth and turnover in progesterone receptor knockout mice. Endocrinology. 2008 May;149(5):2383-2390. https://doi.org/10.1210/en.2007-1247
Rickard, David J. ; Iwaniec, Urszula T. ; Evans, Glenda ; Hefferan, Theresa E. ; Hunter, Jamie C. ; Waters, Katrina M. ; Lydon, John P. ; O'Malley, Bert W. ; Khosla, Sundeep ; Spelsberg, Thomas C. ; Turner, Russell T. / Bone growth and turnover in progesterone receptor knockout mice. In: Endocrinology. 2008 ; Vol. 149, No. 5. pp. 2383-2390.
@article{161c5b52c2ad4959bc6f08c572a71824,
title = "Bone growth and turnover in progesterone receptor knockout mice",
abstract = "The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through thePRis necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain, and tibia longitudinal bone growth were normal in PRKO mice. In contrast, total, cancellous, and cortical bone mass were increased in the humerus of 12-wk-old PRKO mice, whereas cortical and cancellous bone mass in the tibia was normal. At 26 wk of age, cancellous bone area in the proximal tibia metaphysis of PRKO mice was 153{\%} greater than age matched wild-type mice. The improved cancellous bone balance in 6-month-old PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice is not essential for bone growth and turnover. However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence.",
author = "Rickard, {David J.} and Iwaniec, {Urszula T.} and Glenda Evans and Hefferan, {Theresa E.} and Hunter, {Jamie C.} and Waters, {Katrina M.} and Lydon, {John P.} and O'Malley, {Bert W.} and Sundeep Khosla and Spelsberg, {Thomas C.} and Turner, {Russell T.}",
year = "2008",
month = "5",
doi = "10.1210/en.2007-1247",
language = "English (US)",
volume = "149",
pages = "2383--2390",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "5",

}

TY - JOUR

T1 - Bone growth and turnover in progesterone receptor knockout mice

AU - Rickard, David J.

AU - Iwaniec, Urszula T.

AU - Evans, Glenda

AU - Hefferan, Theresa E.

AU - Hunter, Jamie C.

AU - Waters, Katrina M.

AU - Lydon, John P.

AU - O'Malley, Bert W.

AU - Khosla, Sundeep

AU - Spelsberg, Thomas C.

AU - Turner, Russell T.

PY - 2008/5

Y1 - 2008/5

N2 - The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through thePRis necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain, and tibia longitudinal bone growth were normal in PRKO mice. In contrast, total, cancellous, and cortical bone mass were increased in the humerus of 12-wk-old PRKO mice, whereas cortical and cancellous bone mass in the tibia was normal. At 26 wk of age, cancellous bone area in the proximal tibia metaphysis of PRKO mice was 153% greater than age matched wild-type mice. The improved cancellous bone balance in 6-month-old PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice is not essential for bone growth and turnover. However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence.

AB - The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through thePRis necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain, and tibia longitudinal bone growth were normal in PRKO mice. In contrast, total, cancellous, and cortical bone mass were increased in the humerus of 12-wk-old PRKO mice, whereas cortical and cancellous bone mass in the tibia was normal. At 26 wk of age, cancellous bone area in the proximal tibia metaphysis of PRKO mice was 153% greater than age matched wild-type mice. The improved cancellous bone balance in 6-month-old PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice is not essential for bone growth and turnover. However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence.

UR - http://www.scopus.com/inward/record.url?scp=42449154300&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42449154300&partnerID=8YFLogxK

U2 - 10.1210/en.2007-1247

DO - 10.1210/en.2007-1247

M3 - Article

C2 - 18276762

AN - SCOPUS:42449154300

VL - 149

SP - 2383

EP - 2390

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 5

ER -