PMID- 17539737
OWN - NLM
STAT- MEDLINE
DCOM- 20071113
LR  - 20231208
IS  - 0884-0431 (Print)
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 22
IP  - 9
DP  - 2007 Sep
TI  - IGF-I receptor is required for the anabolic actions of parathyroid hormone on 
      bone.
PG  - 1329-37
AB  - We showed that the IGF-IR-null mutation in mature osteoblasts leads to less bone 
      and decreased periosteal bone formation and impaired the stimulatory effects of 
      PTH on osteoprogenitor cell proliferation and differentiation. INTRODUCTION: This 
      study was carried out to examine the role of IGF-I signaling in mediating the 
      actions of PTH on bone. MATERIALS AND METHODS: Three-month-old mice with an 
      osteoblast-specific IGF-I receptor null mutation (IGF-IR OBKO) and their normal 
      littermates were treated with vehicle or PTH (80 microg/kg body weight/d for 2 
      wk). Structural measurements of the proximal and midshaft of the tibia were made 
      by microCT. Trabecular and cortical bone formation was measured by bone 
      histomorphometry. Bone marrow stromal cells (BMSCs) were obtained to assess the 
      effects of PTH on osteoprogenitor number and differentiation. RESULTS: The 
      fat-free weight of bone normalized to body weight (FFW/BW), bone volume (BV/TV), 
      and cortical thickness (C.Th) in both proximal tibia and shaft were all less in 
      the IGF-IR OBKO mice compared with controls. PTH decreased FFW/BW of the proximal 
      tibia more substantially in controls than in IGF-IR OBKO mice. The increase in 
      C.Th after PTH in the proximal tibia was comparable in both control and IGF-IR 
      OBKO mice. Although trabecular and periosteal bone formation was markedly lower 
      in the IGF-IR OBKO mice than in the control mice, endosteal bone formation was 
      comparable in control and IGF-IR OBKO mice. PTH stimulated endosteal bone 
      formation only in the control animals. Compared with BMSCs from control mice, 
      BMSCs from IGF-IR OBKO mice showed equal alkaline phosphatase (ALP)(+) colonies 
      on day 14, but fewer mineralized nodules on day 28. Administration of PTH 
      increased the number of ALP(+) colonies and mineralized nodules on days 14 and 28 
      in BMSCs from control mice, but not in BMSCs from IGF-IR OBKO mice. CONCLUSIONS: 
      Our results indicate that the IGF-IR null mutation in mature osteoblasts leads to 
      less bone and decreased bone formation, in part because of the requirement for 
      the IGF-IR in mature osteoblasts to enable PTH to stimulate osteoprogenitor cell 
      proliferation and differentiation.
FAU - Wang, Yongmei
AU  - Wang Y
AD  - Department of Medicine, Endocrine Unit, Veterans Affairs Medical Center, San 
      Francisco, California 94121, USA.
FAU - Nishida, Shigeki
AU  - Nishida S
FAU - Boudignon, Benjamin M
AU  - Boudignon BM
FAU - Burghardt, Andrew
AU  - Burghardt A
FAU - Elalieh, Hashem Z
AU  - Elalieh HZ
FAU - Hamilton, Michelle M
AU  - Hamilton MM
FAU - Majumdar, Sharmila
AU  - Majumdar S
FAU - Halloran, Bernard P
AU  - Halloran BP
FAU - Clemens, Thomas L
AU  - Clemens TL
FAU - Bikle, Daniel D
AU  - Bikle DD
LA  - eng
GR  - R01 AR055924/AR/NIAMS NIH HHS/United States
GR  - R01 DK054793/DK/NIDDK NIH HHS/United States
GR  - R01 DK54793/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Biomarkers)
RN  - 0 (DNA Primers)
RN  - 0 (Parathyroid Hormone)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Biomarkers/metabolism
MH  - Body Weight
MH  - Bone and Bones/*physiology
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - DNA Primers
MH  - Mice
MH  - Mice, Knockout
MH  - Mutation
MH  - Organ Size
MH  - Parathyroid Hormone/*physiology
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/genetics
MH  - Receptor, IGF Type 1/genetics/metabolism/*physiology
MH  - Signal Transduction
PMC - PMC10702248
MID - NIHMS1948138
COIS- The authors state that they have no conflicts of interest.
EDAT- 2007/06/02 09:00
MHDA- 2007/11/14 09:00
PMCR- 2023/12/07
CRDT- 2007/06/02 09:00
PHST- 2007/06/02 09:00 [pubmed]
PHST- 2007/11/14 09:00 [medline]
PHST- 2007/06/02 09:00 [entrez]
PHST- 2023/12/07 00:00 [pmc-release]
AID - 10.1359/jbmr.070517 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2007 Sep;22(9):1329-37. doi: 10.1359/jbmr.070517.