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

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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 languageEnglish
Pages (from-to)307-313
Number of pages7
Issue number3
StatePublished - 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.


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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology


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