Age-related differences in the expression of receptors for TGF-β in human osteoblast-like cells in vitro

Summary:

The cell surface expression of receptors for TGF-β was studied in human osteoblasts derived from femoral trabecular bone of a total of 19 patients aged 2-83 years. All cell populations investigated showed a similar profile of expression of TGF-β receptors (TβR) I, II and III (betaglycan). There were no significant differences in cell differentiation or proliferative behaviour between the age groups. The TGF-β receptor number per cell significantly increased with age, while the receptor affinity tended to decrease. IGF-I did not influence TβR expression in vitro. The results indicate an age-dependent and IGF-I independent increase of osteoblastic TGF-β receptors in human osteoblast-like cells in vitro.

Key words:

TGF-β - receptor - osteoblast - ageing

References

• 1 Bonewald L F, Dallas S L. Role of active and latent transforming growth factor β in bone formation.  J Cell Biochem. 55 350-357 1994; 
• 2 Canalis E, Pash J, Gabbitas B, Rydziel S, Varghese S. Growth factors regulate the synthesis of insulin-like growth factor I in bone cell cultures.  Endocrinology. 133 33-38 1993; 
• 3 Centrella M, Casinghino S, Ignotz R, McCarthy T L. Multiple regulatory effects by TGF-β on type I collagen levels in osteoblast-enriched cultures from fetal rat bone.  Endocrinology. 131 2863-2872 1992; 
• 4 Centrella M, Casinghino S, Kim J, Pham T, Rosen V, Wozney J, McCarthy T L. Independent changes in type I and type II receptors for TGF-β induced by BMP-2 parallel expression of the osteoblast phenotype.  Mol Cell Biol. 15 3273-3281 1995; 
• 5 Centrella M, Horowitz M C, Wozney J M, McCarthy T L. TGF-β gene family members and bone.  Endocr Rev. 15 27-39 1994; 
• 6 Centrella M, Ji C, Casinghino S, McCarthy T L. Rapid flux in TGF-β receptors on bone cells.  J Biol Chem. 271 18616-18622 1996; 
• 7 Centrella M, McCarthy T L, Canalis E. PTH modulates TGF-β activity and binding in osteoblast-enriched cultures from fetal rat parietal bone.  Proc Natl Acad Sci USA. 85 5889-5893 1988; 
• 8 Eriksen E F, Langdahl B L. The pathogenesis of osteoporosis.  Horm Res. 48 78-82 1997; 
• 9 Falorni A, Bini V, Cabiati G, Papi F, Arzano S, Celi F, Sanasi M. Serum levels of type I procollagen c-terminal propeptide, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 in obese children and adolescents: relationship to gender, pubertal development, growth, insulin, and nutritional status.  Metabolism. 46 862-871 1997; 
• 10 Gebken J, Feydt A, Brinckmann J, Notbohm H, Müller P K, Bätge B. Ligand-induced downregulation of receptors for TGF-β in human osteoblast-like cells from adult donors.  J Endocrinology. 161 503-510 1999; 
• 11 Gebken J, Lüders B, Notbohm H, Klein H H, Brinckmann J, Müller P K, Bätge B. Hypergravity stimulates collagens synthesis in human osteoblast-like cells: evidence for the involvement of p44/42 MAP kinases (ERK1/2).  J Biochem. 126 676-682 1999; 
• 12 Harris S E, Bonewald L F, Harris M A, Sabatini M, Dallas S, Feng J Q, Ghosh-Choudhury N, Wozney J, Mundy G R. Effects of TGF-β on bone nodule formation and expression of BMP-2, osteocalcin, osteopontin, alkaline phosphatase, and type I collagen mRNA in long-term cultures of fetal rat calvarial osteoblasts.  J Bone Mineral Res. 9 855-863 1994; 
• 13 Iimura T, Oida S, Ichijo H, Goseki M, Maruoka Y, Takeda K, Sasaki S. Modulation of responses to TGF-beta by 1, 25 dihydroxyvitamin D3 in MG-63 osteoblastic cells: possible involvement of regulation of TGF-beta type II receptor.  Biochem Biophys Res Commun. 204 918-923 1994; 
• 14 Kruse C, Emmrich J, Rumperl E, Klinger M H, Grünweller A, Rohwedel J, Kramer H J, Kühnel W, Müller P K. Production of trypsin by cells of the exocrine pancreas is paralleled by the expression of the KH protein vigilin.  Exp Cell Research. 239 111-118 1998; 
• 15 Mansell J P, Bailey A J. Abnormal cancellous bone collagen metabolism in osteoarthritis.  J Clin Invest. 101 1596-1603 1998; 
• 16 Massagué J. Identification of receptors for type β transforming growth factor.  Methods Enzymol. 146 174-195 1985; 
• 17 Massagué J. TGF-β signal transduction.  Annu Rev Biochem. 34 753-791 1998; 
• 18 Mohan S, Baylink D J. Insulin-like growth factor system components and the coupling of bone formation to resorption.  Horm Res. 45 59-62 1996; 
• 19 Nicolas V, Prewett A, Bettica P, Mohan S, Finkelman R D, Baylink D J, Farley J R. Age-related decreases in insulin-like growth factor-I and transforming growth factor-beta in femoral cortical bone from both men and women: implications for bone loss with aging.  J Clin Endocrinol Metab. 78 1011-1016 1994; 
• 20 Pfeilschifter J, Diel I, Pilz U, Brunotte K, Naumann A, Ziegler R. Mitogenic responsiveness of human bone cells in vitro to hormones and growth factors decreases with age.  J Bone Mineral Res. 8 707-717 1993; 
• 21 Scatchard G. The attraction of proteins for small molecules and ions.  Ann NY Acad Sci. 51 660-671 1949; 
• 22 Pfeilschifter J, Diel I, Scheppach B, Bretz A, Krempien R, Erdmann J, Schmid G, Reske N, Bismar H, Seck T, Krempien B, Ziegler R. Concentration of TGF-β in human bone tissue: relationship to age, menopause, bone turnover and bone volume.  J Bone Mineral Res. 13 716-730 1998; 
• 23 Seitzer U, Bätge B, Acil Y, Müller P K. Transforming growth factor β ₁ influences lysyl hydroxylation of collagen I and reduces steady-state levels of lysylhydroxylase mRNA in human osteoblast-like cells.  Eur J Clin Invest. 25 959-966 1995; 
• 24 Takeuchi Y, Nakayama K, Matsumoto T. Differentiation and cell surface expression of TGF-β receptors are regulated by interaction with matrix collagen in murine osteoblastic cells.  J Biol Chem. 271 3938-3944 1996;