Abstract
The activities of insulin-like growth factors (IGFs) in bone are modulated by a family of binding proteins (IGFBPs) whose physiological roles remain poorly understood. We have previously shown that targeted overexpression of IGF-I in osteoblasts of transgenic (OC-IGF-I) mice stimulates bone formation. In this model, bone formation is markedly but transiently increased in an age-dependent manner, raising the possibility that IGF-I may be influencing IGFBPs to in turn modulate its paracrine actions within bone. We sought to characterize the IGFBPs in normal mouse bone during development and to determine whether osteoblast-targeted overexpression of IGF-I influenced bone IGFBP abundance in vivo. Femoral bone IGFBP content was assessed in control nontransgenic and OC-IGF-I mice by I125-IGF-I ligand and immunoblotting. Bone IGFBP-5 and IGF-I mRNA abundance was determined using real-time reverse transcription (RT)-PCR. Ligand blot of bone extract showed a 30-kDa band, identified as IGFBP-5 by immunoblot, predominated. The abundance of IGFBP-5 declined with age in both control and transgenic bone. Ligand and immunoblot analysis revealed a 5-fold increase in IGFBP-5 protein levels at 3 weeks in transgenic bone (P <0.0001). The elevated IGFBP-5 protein levels were associated with a similar increase in IGF-I mRNA abundance (4-fold, P <0.01) and a significant increase in IGFBP-5 mRNA abundance (1.5-fold). Despite the age-related decline at 6 weeks, IGFBP-5 remained significantly (P <0.01) more abundant in transgenic bone compared to controls. In contrast, bone IGFBP-4 abundance was relatively unchanged by either age or IGF-I overexpression. These studies demonstrate a distinctive developmental pattern of IGFBP-5 content in mouse bone and show that osteoblast-derived IGF-I determines skeletal IGFBP-5 abundance, at least in part by inducing its synthesis. In that IGFBP-5 is thought to stimulate bone formation, directly or via IGF-I action, such changes in bone IGFBP-5 may be important to ensure robust bone acquisition in the early postnatal period.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 224-231 |
| Number of pages | 8 |
| Journal | Bone |
| Volume | 36 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2005 |
| Externally published | Yes |
Fingerprint
Keywords
- Bone formation
- Insulin-like growth factor (IGF-I)
- Insulin-like growth factor binding protein (IGFBP)
- Paracrine regulation
- Transgenic mice
ASJC Scopus subject areas
- Physiology
- Hematology
Cite this
Osteoblast-specific expression of insulin-like growth factor-1 in bone of transgenic mice induces insulin-like growth factor binding protein-5. / Rutter, Meilan M.; Markoff, Edith; Clayton, Lisa; Akeno, Nagako; Zhao, Guisheng; Clemens, Thomas; Chernausek, Steven D.
In: Bone, Vol. 36, No. 2, 02.2005, p. 224-231.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Osteoblast-specific expression of insulin-like growth factor-1 in bone of transgenic mice induces insulin-like growth factor binding protein-5
AU - Rutter, Meilan M.
AU - Markoff, Edith
AU - Clayton, Lisa
AU - Akeno, Nagako
AU - Zhao, Guisheng
AU - Clemens, Thomas
AU - Chernausek, Steven D.
PY - 2005/2
Y1 - 2005/2
N2 - The activities of insulin-like growth factors (IGFs) in bone are modulated by a family of binding proteins (IGFBPs) whose physiological roles remain poorly understood. We have previously shown that targeted overexpression of IGF-I in osteoblasts of transgenic (OC-IGF-I) mice stimulates bone formation. In this model, bone formation is markedly but transiently increased in an age-dependent manner, raising the possibility that IGF-I may be influencing IGFBPs to in turn modulate its paracrine actions within bone. We sought to characterize the IGFBPs in normal mouse bone during development and to determine whether osteoblast-targeted overexpression of IGF-I influenced bone IGFBP abundance in vivo. Femoral bone IGFBP content was assessed in control nontransgenic and OC-IGF-I mice by I125-IGF-I ligand and immunoblotting. Bone IGFBP-5 and IGF-I mRNA abundance was determined using real-time reverse transcription (RT)-PCR. Ligand blot of bone extract showed a 30-kDa band, identified as IGFBP-5 by immunoblot, predominated. The abundance of IGFBP-5 declined with age in both control and transgenic bone. Ligand and immunoblot analysis revealed a 5-fold increase in IGFBP-5 protein levels at 3 weeks in transgenic bone (P <0.0001). The elevated IGFBP-5 protein levels were associated with a similar increase in IGF-I mRNA abundance (4-fold, P <0.01) and a significant increase in IGFBP-5 mRNA abundance (1.5-fold). Despite the age-related decline at 6 weeks, IGFBP-5 remained significantly (P <0.01) more abundant in transgenic bone compared to controls. In contrast, bone IGFBP-4 abundance was relatively unchanged by either age or IGF-I overexpression. These studies demonstrate a distinctive developmental pattern of IGFBP-5 content in mouse bone and show that osteoblast-derived IGF-I determines skeletal IGFBP-5 abundance, at least in part by inducing its synthesis. In that IGFBP-5 is thought to stimulate bone formation, directly or via IGF-I action, such changes in bone IGFBP-5 may be important to ensure robust bone acquisition in the early postnatal period.
AB - The activities of insulin-like growth factors (IGFs) in bone are modulated by a family of binding proteins (IGFBPs) whose physiological roles remain poorly understood. We have previously shown that targeted overexpression of IGF-I in osteoblasts of transgenic (OC-IGF-I) mice stimulates bone formation. In this model, bone formation is markedly but transiently increased in an age-dependent manner, raising the possibility that IGF-I may be influencing IGFBPs to in turn modulate its paracrine actions within bone. We sought to characterize the IGFBPs in normal mouse bone during development and to determine whether osteoblast-targeted overexpression of IGF-I influenced bone IGFBP abundance in vivo. Femoral bone IGFBP content was assessed in control nontransgenic and OC-IGF-I mice by I125-IGF-I ligand and immunoblotting. Bone IGFBP-5 and IGF-I mRNA abundance was determined using real-time reverse transcription (RT)-PCR. Ligand blot of bone extract showed a 30-kDa band, identified as IGFBP-5 by immunoblot, predominated. The abundance of IGFBP-5 declined with age in both control and transgenic bone. Ligand and immunoblot analysis revealed a 5-fold increase in IGFBP-5 protein levels at 3 weeks in transgenic bone (P <0.0001). The elevated IGFBP-5 protein levels were associated with a similar increase in IGF-I mRNA abundance (4-fold, P <0.01) and a significant increase in IGFBP-5 mRNA abundance (1.5-fold). Despite the age-related decline at 6 weeks, IGFBP-5 remained significantly (P <0.01) more abundant in transgenic bone compared to controls. In contrast, bone IGFBP-4 abundance was relatively unchanged by either age or IGF-I overexpression. These studies demonstrate a distinctive developmental pattern of IGFBP-5 content in mouse bone and show that osteoblast-derived IGF-I determines skeletal IGFBP-5 abundance, at least in part by inducing its synthesis. In that IGFBP-5 is thought to stimulate bone formation, directly or via IGF-I action, such changes in bone IGFBP-5 may be important to ensure robust bone acquisition in the early postnatal period.
KW - Bone formation
KW - Insulin-like growth factor (IGF-I)
KW - Insulin-like growth factor binding protein (IGFBP)
KW - Paracrine regulation
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=14144249534&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14144249534&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2004.10.005
DO - 10.1016/j.bone.2004.10.005
M3 - Article
C2 - 15780948
AN - SCOPUS:14144249534
VL - 36
SP - 224
EP - 231
JO - Bone
JF - Bone
SN - 8756-3282
IS - 2
ER -