Differentiation of MC3T3-E1 Osteoblasts is associated with temporal changes in the expression of IGF-I and IGFBPs

K. M. Thrailkill; S. R. Siddhanti; J. L. Fowlkes; L. D. Quarles

doi:10.1016/8756-3282(95)00223-Z

Differentiation of MC3T3-E1 Osteoblasts is associated with temporal changes in the expression of IGF-I and IGFBPs

K. M. Thrailkill, S. R. Siddhanti, J. L. Fowlkes, L. D. Quarles

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29 Scopus citations

Abstract

We examined the relationship between osteoblast maturation and temporal changes in the secretion of IGF-I and the IGF-binding proteins (IGFBPs) in the MC3T3-El model of osteoblast development. IGF-I was present at low levels in conditioned media in proliferating preosteoblasts (3.7 ± 1.7 ng/μg DNA and 3.9 ± 0.6 at culture (days 3 and 9) and increased progressively in postmitotic differentiating osteoblasts, reaching a maximal concentration of 13.1 ± 1.5 ng/μg DNA by day 25 of culture. We also observed an increase in IGF-I mRNA expression. Using Western ligand blot and immunoblot techniques, we found that IGFBP-2, -4, and -5 also displayed temporal differences in expression during MC3T3-El development. We observed a sustained increase in IGFBP-2, -4, and -5 mRNA expression between days 10-14, coincident with the onset of differentiation. IGFBP-2 and IGFBP-4 protein concentrations increased in parallel with IGFBP mRNA expression, but IGFBP-5 levels peaked between days 1-14 of culture, and declined thereafter in spite of persistent IGFBP-5 mRNA levels. These findings suggest complex transcriptional and post-transcriptional regulation of IGFBP metabolism during osteoblast development. Thus, IGF-I and IGFBP production are regulated during osteoblast development. In turn, time-dependent changes in IGF-I and modulation of IGF-I bioavailability by IGFBPs may regulate the osteoblastic developmental sequence.

Original language	English
Pages (from-to)	307-313
Number of pages	7
Journal	Bone
Volume	17
Issue number	3
DOIs	https://doi.org/10.1016/8756-3282(95)00223-Z
State	Published - Sep 1995

Bibliographical note

Funding Information:
Acknowledgmenrs: This work was supported by a Duke Children’s Telethon grant (K.M.T) and Grant No. AR37308 from the National Institutes of Arthritis and Musculoskeletal and Skin Diseases (L.D.Q). The authors are grateful to Dr. David Clemmons, Dr. Christopher Maack, and Dr. Michael Keifer for providing the various IGFBP antisera used in these studies. The authors also thank Phyllis Driscoll and Jian Zhang for technical assistance and Cristy McGranahan for secretarial assistance.

Keywords

Insulin-like growth factor binding proteins
Insulin-like growth factors
Osteoblast development

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Physiology
Histology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/8756-3282(95)00223-Z

Cite this

@article{c7257140b18c48ceb8fd758bb7e449ef,

title = "Differentiation of MC3T3-E1 Osteoblasts is associated with temporal changes in the expression of IGF-I and IGFBPs",

abstract = "We examined the relationship between osteoblast maturation and temporal changes in the secretion of IGF-I and the IGF-binding proteins (IGFBPs) in the MC3T3-El model of osteoblast development. IGF-I was present at low levels in conditioned media in proliferating preosteoblasts (3.7 ± 1.7 ng/μg DNA and 3.9 ± 0.6 at culture (days 3 and 9) and increased progressively in postmitotic differentiating osteoblasts, reaching a maximal concentration of 13.1 ± 1.5 ng/μg DNA by day 25 of culture. We also observed an increase in IGF-I mRNA expression. Using Western ligand blot and immunoblot techniques, we found that IGFBP-2, -4, and -5 also displayed temporal differences in expression during MC3T3-El development. We observed a sustained increase in IGFBP-2, -4, and -5 mRNA expression between days 10-14, coincident with the onset of differentiation. IGFBP-2 and IGFBP-4 protein concentrations increased in parallel with IGFBP mRNA expression, but IGFBP-5 levels peaked between days 1-14 of culture, and declined thereafter in spite of persistent IGFBP-5 mRNA levels. These findings suggest complex transcriptional and post-transcriptional regulation of IGFBP metabolism during osteoblast development. Thus, IGF-I and IGFBP production are regulated during osteoblast development. In turn, time-dependent changes in IGF-I and modulation of IGF-I bioavailability by IGFBPs may regulate the osteoblastic developmental sequence.",

keywords = "Insulin-like growth factor binding proteins, Insulin-like growth factors, Osteoblast development",

author = "Thrailkill, {K. M.} and Siddhanti, {S. R.} and Fowlkes, {J. L.} and Quarles, {L. D.}",

note = "Funding Information: Acknowledgmenrs: This work was supported by a Duke Children{\textquoteright}s Telethon grant (K.M.T) and Grant No. AR37308 from the National Institutes of Arthritis and Musculoskeletal and Skin Diseases (L.D.Q). The authors are grateful to Dr. David Clemmons, Dr. Christopher Maack, and Dr. Michael Keifer for providing the various IGFBP antisera used in these studies. The authors also thank Phyllis Driscoll and Jian Zhang for technical assistance and Cristy McGranahan for secretarial assistance.",

year = "1995",

month = sep,

doi = "10.1016/8756-3282(95)00223-Z",

language = "English",

volume = "17",

pages = "307--313",

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T1 - Differentiation of MC3T3-E1 Osteoblasts is associated with temporal changes in the expression of IGF-I and IGFBPs

AU - Thrailkill, K. M.

AU - Siddhanti, S. R.

AU - Fowlkes, J. L.

AU - Quarles, L. D.

N1 - Funding Information: Acknowledgmenrs: This work was supported by a Duke Children’s Telethon grant (K.M.T) and Grant No. AR37308 from the National Institutes of Arthritis and Musculoskeletal and Skin Diseases (L.D.Q). The authors are grateful to Dr. David Clemmons, Dr. Christopher Maack, and Dr. Michael Keifer for providing the various IGFBP antisera used in these studies. The authors also thank Phyllis Driscoll and Jian Zhang for technical assistance and Cristy McGranahan for secretarial assistance.

PY - 1995/9

Y1 - 1995/9

N2 - We examined the relationship between osteoblast maturation and temporal changes in the secretion of IGF-I and the IGF-binding proteins (IGFBPs) in the MC3T3-El model of osteoblast development. IGF-I was present at low levels in conditioned media in proliferating preosteoblasts (3.7 ± 1.7 ng/μg DNA and 3.9 ± 0.6 at culture (days 3 and 9) and increased progressively in postmitotic differentiating osteoblasts, reaching a maximal concentration of 13.1 ± 1.5 ng/μg DNA by day 25 of culture. We also observed an increase in IGF-I mRNA expression. Using Western ligand blot and immunoblot techniques, we found that IGFBP-2, -4, and -5 also displayed temporal differences in expression during MC3T3-El development. We observed a sustained increase in IGFBP-2, -4, and -5 mRNA expression between days 10-14, coincident with the onset of differentiation. IGFBP-2 and IGFBP-4 protein concentrations increased in parallel with IGFBP mRNA expression, but IGFBP-5 levels peaked between days 1-14 of culture, and declined thereafter in spite of persistent IGFBP-5 mRNA levels. These findings suggest complex transcriptional and post-transcriptional regulation of IGFBP metabolism during osteoblast development. Thus, IGF-I and IGFBP production are regulated during osteoblast development. In turn, time-dependent changes in IGF-I and modulation of IGF-I bioavailability by IGFBPs may regulate the osteoblastic developmental sequence.

AB - We examined the relationship between osteoblast maturation and temporal changes in the secretion of IGF-I and the IGF-binding proteins (IGFBPs) in the MC3T3-El model of osteoblast development. IGF-I was present at low levels in conditioned media in proliferating preosteoblasts (3.7 ± 1.7 ng/μg DNA and 3.9 ± 0.6 at culture (days 3 and 9) and increased progressively in postmitotic differentiating osteoblasts, reaching a maximal concentration of 13.1 ± 1.5 ng/μg DNA by day 25 of culture. We also observed an increase in IGF-I mRNA expression. Using Western ligand blot and immunoblot techniques, we found that IGFBP-2, -4, and -5 also displayed temporal differences in expression during MC3T3-El development. We observed a sustained increase in IGFBP-2, -4, and -5 mRNA expression between days 10-14, coincident with the onset of differentiation. IGFBP-2 and IGFBP-4 protein concentrations increased in parallel with IGFBP mRNA expression, but IGFBP-5 levels peaked between days 1-14 of culture, and declined thereafter in spite of persistent IGFBP-5 mRNA levels. These findings suggest complex transcriptional and post-transcriptional regulation of IGFBP metabolism during osteoblast development. Thus, IGF-I and IGFBP production are regulated during osteoblast development. In turn, time-dependent changes in IGF-I and modulation of IGF-I bioavailability by IGFBPs may regulate the osteoblastic developmental sequence.

KW - Insulin-like growth factor binding proteins

KW - Insulin-like growth factors

KW - Osteoblast development

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DO - 10.1016/8756-3282(95)00223-Z

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VL - 17

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ER -

Differentiation of MC3T3-E1 Osteoblasts is associated with temporal changes in the expression of IGF-I and IGFBPs

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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