Targeting simian virus 40 T antigen to the osteoclast in transgenic mice causes osteoclast tumors and transformation and apoptosis of osteoclasts

B. F. Boyce, K. Wright, S. V. Reddy, B. A. Koop, B. Story, R. Devlin, R. J. Leach, G. David Roodman, J. L. Windle

Research output: Contribution to journalArticle

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Abstract

Osteoclasts are terminally differentiated cells that express tartrate- resistant acid phosphatase (TRAP) at a higher level than other normal cells. Therefore, in an attempt to develop immortalized osteoclasts, we produced two lines of transgenic mice in which expression of the simian virus 40 T antigen oncogene was targeted to osteoclasts using the TRAP gene promoter. Osteoclasts were increased in number in bones from both lines. More than 50% of them appeared morphologically transformed, 2-5% were mitotic, but, unexpectedly, 5% were apoptotic. Osteoclast tumors were observed occasionally in one line of mice (line 4), and sheets of TRAP-positive cells (tumorlets) developed in most mice in both lines. Although cells isolated from these tumorlets formed multinucleated TRAP-positive cells that resorbed bone in vitro, to date we have been unable to develop an immortalized osteoclast cell line from them. Osteoclasts from one line (line 5) had reduced ruffled border formation and a higher level of T-antigen expression than osteoclasts in the other line (line 4), and these features were associated with the presence of osteopetrosis. However, osteoclasts from these osteopetrotic mice and from line 4 mice resorbed bone normally when the mice were treated with interleukin-1. These findings indicate that T antigen can be targeted to osteoclasts in transgenic mice and causes osteoclast transformation, tumors, mitosis, and apoptosis. When T antigen is expressed at high levels, functional impairment of osteoclasts can be detected. Furthermore, these results suggest that T antigen is insufficient on its own to immortalize cells in the osteoclast lineage.

Original languageEnglish (US)
Pages (from-to)5751-5759
Number of pages9
JournalEndocrinology
Volume136
Issue number12
StatePublished - 1995
Externally publishedYes

Fingerprint

Simian virus 40
Viral Tumor Antigens
Osteoclasts
Transgenic Mice
Apoptosis
Neoplasms
Bone and Bones
Osteopetrosis
Interleukin-1
Oncogenes
Mitosis

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Boyce, B. F., Wright, K., Reddy, S. V., Koop, B. A., Story, B., Devlin, R., ... Windle, J. L. (1995). Targeting simian virus 40 T antigen to the osteoclast in transgenic mice causes osteoclast tumors and transformation and apoptosis of osteoclasts. Endocrinology, 136(12), 5751-5759.

Targeting simian virus 40 T antigen to the osteoclast in transgenic mice causes osteoclast tumors and transformation and apoptosis of osteoclasts. / Boyce, B. F.; Wright, K.; Reddy, S. V.; Koop, B. A.; Story, B.; Devlin, R.; Leach, R. J.; Roodman, G. David; Windle, J. L.

In: Endocrinology, Vol. 136, No. 12, 1995, p. 5751-5759.

Research output: Contribution to journalArticle

Boyce, BF, Wright, K, Reddy, SV, Koop, BA, Story, B, Devlin, R, Leach, RJ, Roodman, GD & Windle, JL 1995, 'Targeting simian virus 40 T antigen to the osteoclast in transgenic mice causes osteoclast tumors and transformation and apoptosis of osteoclasts', Endocrinology, vol. 136, no. 12, pp. 5751-5759.
Boyce, B. F. ; Wright, K. ; Reddy, S. V. ; Koop, B. A. ; Story, B. ; Devlin, R. ; Leach, R. J. ; Roodman, G. David ; Windle, J. L. / Targeting simian virus 40 T antigen to the osteoclast in transgenic mice causes osteoclast tumors and transformation and apoptosis of osteoclasts. In: Endocrinology. 1995 ; Vol. 136, No. 12. pp. 5751-5759.
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AU - Boyce, B. F.

AU - Wright, K.

AU - Reddy, S. V.

AU - Koop, B. A.

AU - Story, B.

AU - Devlin, R.

AU - Leach, R. J.

AU - Roodman, G. David

AU - Windle, J. L.

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