Combined effects of insulin-like growth factor-1 and transforming growth factor-β1 on periosteal mesenchymal cells during chondrogenesis in vitro

T. Fukumoto, J. W. Sperling, A. Sanyal, J. S. Fitzsimmons, G. G. Reinholz, Cheryl A Conover, Shawn W. O'Driscoll

Research output: Contribution to journalArticle

212 Citations (Scopus)

Abstract

Objective: Periosteum contains undifferentiated mesenchymal stem cells that have both chondrogenic and osteogenic potential, and has been used to repair articular cartilage defects. During this process, the role of growth factors that stimulate the periosteal mesenchymal cells toward chondrogenesis to regenerate articular cartilage and maintain its phenotype is not yet fully understood. In this study, we examined the effects of insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1), alone and in combination, on periosteal chondrogenesis using an in vitro organ culture model. Methods: Periosteal explants from the medial proximal tibia of 2-month-old rabbits were cultured in agarose under serum free conditions for up to 6 weeks. After culture the explants were weighed, assayed for cartilage production via Safranin O staining and histomorphometry, assessed for proliferation via proliferative cell nuclear antigen (PCNA) immunostaining, and assessed for type II collagen mRNA expression via in situ hybridization. Results: IGF-1 significantly increased chondrogenesis in a dose-dependent manner when administered continuously throughout the culture period. Continuous IGF-1, in combination with TGF-β1 for the first 2 days, further enhanced overall total cartilage growth. Immunohistochemistry for PCNA revealed that combining IGF-1 with TGF-β1 gave the strongest proliferative stimulus early during chondrogenesis. In situ hybridization for type II collagen showed that continuous IGF-1 maintained type II collagen mRNA expression throughout the cambium layer from 2 to 6 weeks. Conclusion: The results of this study demonstrate that IGF-1 and TGF-β1 can act in combination to regulate proliferation and differentiation of periosteal mesenchymal cells during chondrogenesis.

Original languageEnglish (US)
Pages (from-to)55-64
Number of pages10
JournalOsteoarthritis and Cartilage
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2003

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Chondrogenesis
Insulin
Transforming Growth Factors
Somatomedins
Collagen Type II
Nuclear Antigens
Cartilage
Articular Cartilage
In Situ Hybridization
Collagen
Cambium
Periosteum
Messenger RNA
Antigens
Organ Culture Techniques
Tibia
Mesenchymal Stromal Cells
Sepharose
In Vitro Techniques
Intercellular Signaling Peptides and Proteins

Keywords

  • Chondrogenesis
  • IGF-1
  • Periosteum
  • Proliferation
  • TGF-β1

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Combined effects of insulin-like growth factor-1 and transforming growth factor-β1 on periosteal mesenchymal cells during chondrogenesis in vitro. / Fukumoto, T.; Sperling, J. W.; Sanyal, A.; Fitzsimmons, J. S.; Reinholz, G. G.; Conover, Cheryl A; O'Driscoll, Shawn W.

In: Osteoarthritis and Cartilage, Vol. 11, No. 1, 01.01.2003, p. 55-64.

Research output: Contribution to journalArticle

Fukumoto, T. ; Sperling, J. W. ; Sanyal, A. ; Fitzsimmons, J. S. ; Reinholz, G. G. ; Conover, Cheryl A ; O'Driscoll, Shawn W. / Combined effects of insulin-like growth factor-1 and transforming growth factor-β1 on periosteal mesenchymal cells during chondrogenesis in vitro. In: Osteoarthritis and Cartilage. 2003 ; Vol. 11, No. 1. pp. 55-64.
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AU - Fukumoto, T.

AU - Sperling, J. W.

AU - Sanyal, A.

AU - Fitzsimmons, J. S.

AU - Reinholz, G. G.

AU - Conover, Cheryl A

AU - O'Driscoll, Shawn W.

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AB - Objective: Periosteum contains undifferentiated mesenchymal stem cells that have both chondrogenic and osteogenic potential, and has been used to repair articular cartilage defects. During this process, the role of growth factors that stimulate the periosteal mesenchymal cells toward chondrogenesis to regenerate articular cartilage and maintain its phenotype is not yet fully understood. In this study, we examined the effects of insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1), alone and in combination, on periosteal chondrogenesis using an in vitro organ culture model. Methods: Periosteal explants from the medial proximal tibia of 2-month-old rabbits were cultured in agarose under serum free conditions for up to 6 weeks. After culture the explants were weighed, assayed for cartilage production via Safranin O staining and histomorphometry, assessed for proliferation via proliferative cell nuclear antigen (PCNA) immunostaining, and assessed for type II collagen mRNA expression via in situ hybridization. Results: IGF-1 significantly increased chondrogenesis in a dose-dependent manner when administered continuously throughout the culture period. Continuous IGF-1, in combination with TGF-β1 for the first 2 days, further enhanced overall total cartilage growth. Immunohistochemistry for PCNA revealed that combining IGF-1 with TGF-β1 gave the strongest proliferative stimulus early during chondrogenesis. In situ hybridization for type II collagen showed that continuous IGF-1 maintained type II collagen mRNA expression throughout the cambium layer from 2 to 6 weeks. Conclusion: The results of this study demonstrate that IGF-1 and TGF-β1 can act in combination to regulate proliferation and differentiation of periosteal mesenchymal cells during chondrogenesis.

KW - Chondrogenesis

KW - IGF-1

KW - Periosteum

KW - Proliferation

KW - TGF-β1

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