Impact of glucose-dependent insulinotropic peptide on age-induced bone loss

Kehong Ding, Xing Ming Shi, Qing Zhong, Baolin Kang, Ding Xie, Wendy B Bollag, Roni Jacob Bollag, William D Hill, Walter Washington, Qing Sheng Mi, Karl Insogna, Norman Chutkan, Mark W Hamrick, Carlos M Isales

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

GIP is an important hormonal link between nutrition and bone formation. We show for the first time that BMSCs express functional GIP receptors, that expression decreases with aging, and that elevations in GIP can prevent age-associated bone loss. Introduction: We previously showed that C57BL/6 mice lose bone mass as they age, particularly between 18 and 24 mo of age. The mechanisms involved in this age-dependent induced bone loss are probably multifactorial, but adequate nutrition and nutritional signals seem to be important. Glucose-dependent insulinotropic peptide (GIP) is an enteric hormone whose receptors are present in osteoblasts, and GIP is known to stimulate osteoblastic activity in vitro. In vivo, GIP-overexpressing C57BL/6 transgenic (GIP Tg+) mice have increased bone mass compared with controls. Bone histomorphometric data suggest that GIP increases osteoblast number, possibly by preventing osteoblastic apoptosis. However, potential GIP effects on osteoblastic precursors, bone marrow stromal cells (BMSCs), had not previously been examined. In addition, effects of GIP on age-induced bone loss were not known. Materials and Methods: Changes in BMD, biomechanics, biomarkers of bone turnover, and bone histology were assessed in C57BL/6 GIP Tg+ versus Tg- (littermate) mice between the ages of 1 and 24 mo of age. In addition, age-related changes in GIP receptor (GIPR) expression and GIP effects on differentiation of BMSCs were also assessed as potential causal factors in aging-induced bone loss. Results: We report that bone mass and bone strength in GIP Tg+ mice did not drop in a similar age-dependent fashion as in controls. In addition, biomarker measurements showed that GIP Tg+ mice had increased osteoblastic activity compared with wildtype control mice. Finally, we report for the first time that BMSCs express GIPR, that the expression decreases in an age-dependent manner, and that stimulation of BMSCs with GIP led to increased osteoblastic differentiation. Conclusions: Our data show that elevated GIP levels prevent age-related loss of bone mass and bone strength and suggest that age-related decreases in GIP receptor expression in BMSCs may play a pathophysiological role in this bone loss. We conclude that elevations in GIP may be an effective countermeasure to age-induced bone loss.

Original languageEnglish (US)
Pages (from-to)536-543
Number of pages8
JournalJournal of Bone and Mineral Research
Volume23
Issue number4
DOIs
StatePublished - Apr 1 2008

Fingerprint

Gastric Inhibitory Polypeptide
Bone and Bones
Mesenchymal Stromal Cells
Peptide Receptors
Osteoblasts
Biomarkers

Keywords

  • Aging
  • Bone
  • Bone marrow stromal cells
  • Glucose-dependent insulinotropic peptide
  • Transgenic mice

ASJC Scopus subject areas

  • Surgery

Cite this

Impact of glucose-dependent insulinotropic peptide on age-induced bone loss. / Ding, Kehong; Shi, Xing Ming; Zhong, Qing; Kang, Baolin; Xie, Ding; Bollag, Wendy B; Bollag, Roni Jacob; Hill, William D; Washington, Walter; Mi, Qing Sheng; Insogna, Karl; Chutkan, Norman; Hamrick, Mark W; Isales, Carlos M.

In: Journal of Bone and Mineral Research, Vol. 23, No. 4, 01.04.2008, p. 536-543.

Research output: Contribution to journalArticle

@article{899be42cbc9c42aca22edd94962aa1e4,
title = "Impact of glucose-dependent insulinotropic peptide on age-induced bone loss",
abstract = "GIP is an important hormonal link between nutrition and bone formation. We show for the first time that BMSCs express functional GIP receptors, that expression decreases with aging, and that elevations in GIP can prevent age-associated bone loss. Introduction: We previously showed that C57BL/6 mice lose bone mass as they age, particularly between 18 and 24 mo of age. The mechanisms involved in this age-dependent induced bone loss are probably multifactorial, but adequate nutrition and nutritional signals seem to be important. Glucose-dependent insulinotropic peptide (GIP) is an enteric hormone whose receptors are present in osteoblasts, and GIP is known to stimulate osteoblastic activity in vitro. In vivo, GIP-overexpressing C57BL/6 transgenic (GIP Tg+) mice have increased bone mass compared with controls. Bone histomorphometric data suggest that GIP increases osteoblast number, possibly by preventing osteoblastic apoptosis. However, potential GIP effects on osteoblastic precursors, bone marrow stromal cells (BMSCs), had not previously been examined. In addition, effects of GIP on age-induced bone loss were not known. Materials and Methods: Changes in BMD, biomechanics, biomarkers of bone turnover, and bone histology were assessed in C57BL/6 GIP Tg+ versus Tg- (littermate) mice between the ages of 1 and 24 mo of age. In addition, age-related changes in GIP receptor (GIPR) expression and GIP effects on differentiation of BMSCs were also assessed as potential causal factors in aging-induced bone loss. Results: We report that bone mass and bone strength in GIP Tg+ mice did not drop in a similar age-dependent fashion as in controls. In addition, biomarker measurements showed that GIP Tg+ mice had increased osteoblastic activity compared with wildtype control mice. Finally, we report for the first time that BMSCs express GIPR, that the expression decreases in an age-dependent manner, and that stimulation of BMSCs with GIP led to increased osteoblastic differentiation. Conclusions: Our data show that elevated GIP levels prevent age-related loss of bone mass and bone strength and suggest that age-related decreases in GIP receptor expression in BMSCs may play a pathophysiological role in this bone loss. We conclude that elevations in GIP may be an effective countermeasure to age-induced bone loss.",
keywords = "Aging, Bone, Bone marrow stromal cells, Glucose-dependent insulinotropic peptide, Transgenic mice",
author = "Kehong Ding and Shi, {Xing Ming} and Qing Zhong and Baolin Kang and Ding Xie and Bollag, {Wendy B} and Bollag, {Roni Jacob} and Hill, {William D} and Walter Washington and Mi, {Qing Sheng} and Karl Insogna and Norman Chutkan and Hamrick, {Mark W} and Isales, {Carlos M}",
year = "2008",
month = "4",
day = "1",
doi = "10.1359/jbmr.071202",
language = "English (US)",
volume = "23",
pages = "536--543",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Impact of glucose-dependent insulinotropic peptide on age-induced bone loss

AU - Ding, Kehong

AU - Shi, Xing Ming

AU - Zhong, Qing

AU - Kang, Baolin

AU - Xie, Ding

AU - Bollag, Wendy B

AU - Bollag, Roni Jacob

AU - Hill, William D

AU - Washington, Walter

AU - Mi, Qing Sheng

AU - Insogna, Karl

AU - Chutkan, Norman

AU - Hamrick, Mark W

AU - Isales, Carlos M

PY - 2008/4/1

Y1 - 2008/4/1

N2 - GIP is an important hormonal link between nutrition and bone formation. We show for the first time that BMSCs express functional GIP receptors, that expression decreases with aging, and that elevations in GIP can prevent age-associated bone loss. Introduction: We previously showed that C57BL/6 mice lose bone mass as they age, particularly between 18 and 24 mo of age. The mechanisms involved in this age-dependent induced bone loss are probably multifactorial, but adequate nutrition and nutritional signals seem to be important. Glucose-dependent insulinotropic peptide (GIP) is an enteric hormone whose receptors are present in osteoblasts, and GIP is known to stimulate osteoblastic activity in vitro. In vivo, GIP-overexpressing C57BL/6 transgenic (GIP Tg+) mice have increased bone mass compared with controls. Bone histomorphometric data suggest that GIP increases osteoblast number, possibly by preventing osteoblastic apoptosis. However, potential GIP effects on osteoblastic precursors, bone marrow stromal cells (BMSCs), had not previously been examined. In addition, effects of GIP on age-induced bone loss were not known. Materials and Methods: Changes in BMD, biomechanics, biomarkers of bone turnover, and bone histology were assessed in C57BL/6 GIP Tg+ versus Tg- (littermate) mice between the ages of 1 and 24 mo of age. In addition, age-related changes in GIP receptor (GIPR) expression and GIP effects on differentiation of BMSCs were also assessed as potential causal factors in aging-induced bone loss. Results: We report that bone mass and bone strength in GIP Tg+ mice did not drop in a similar age-dependent fashion as in controls. In addition, biomarker measurements showed that GIP Tg+ mice had increased osteoblastic activity compared with wildtype control mice. Finally, we report for the first time that BMSCs express GIPR, that the expression decreases in an age-dependent manner, and that stimulation of BMSCs with GIP led to increased osteoblastic differentiation. Conclusions: Our data show that elevated GIP levels prevent age-related loss of bone mass and bone strength and suggest that age-related decreases in GIP receptor expression in BMSCs may play a pathophysiological role in this bone loss. We conclude that elevations in GIP may be an effective countermeasure to age-induced bone loss.

AB - GIP is an important hormonal link between nutrition and bone formation. We show for the first time that BMSCs express functional GIP receptors, that expression decreases with aging, and that elevations in GIP can prevent age-associated bone loss. Introduction: We previously showed that C57BL/6 mice lose bone mass as they age, particularly between 18 and 24 mo of age. The mechanisms involved in this age-dependent induced bone loss are probably multifactorial, but adequate nutrition and nutritional signals seem to be important. Glucose-dependent insulinotropic peptide (GIP) is an enteric hormone whose receptors are present in osteoblasts, and GIP is known to stimulate osteoblastic activity in vitro. In vivo, GIP-overexpressing C57BL/6 transgenic (GIP Tg+) mice have increased bone mass compared with controls. Bone histomorphometric data suggest that GIP increases osteoblast number, possibly by preventing osteoblastic apoptosis. However, potential GIP effects on osteoblastic precursors, bone marrow stromal cells (BMSCs), had not previously been examined. In addition, effects of GIP on age-induced bone loss were not known. Materials and Methods: Changes in BMD, biomechanics, biomarkers of bone turnover, and bone histology were assessed in C57BL/6 GIP Tg+ versus Tg- (littermate) mice between the ages of 1 and 24 mo of age. In addition, age-related changes in GIP receptor (GIPR) expression and GIP effects on differentiation of BMSCs were also assessed as potential causal factors in aging-induced bone loss. Results: We report that bone mass and bone strength in GIP Tg+ mice did not drop in a similar age-dependent fashion as in controls. In addition, biomarker measurements showed that GIP Tg+ mice had increased osteoblastic activity compared with wildtype control mice. Finally, we report for the first time that BMSCs express GIPR, that the expression decreases in an age-dependent manner, and that stimulation of BMSCs with GIP led to increased osteoblastic differentiation. Conclusions: Our data show that elevated GIP levels prevent age-related loss of bone mass and bone strength and suggest that age-related decreases in GIP receptor expression in BMSCs may play a pathophysiological role in this bone loss. We conclude that elevations in GIP may be an effective countermeasure to age-induced bone loss.

KW - Aging

KW - Bone

KW - Bone marrow stromal cells

KW - Glucose-dependent insulinotropic peptide

KW - Transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=41849094819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41849094819&partnerID=8YFLogxK

U2 - 10.1359/jbmr.071202

DO - 10.1359/jbmr.071202

M3 - Article

VL - 23

SP - 536

EP - 543

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 4

ER -