Marshall Digital Scholar

Title

Differential Regulation of Osteoblast Activity by Th Cell Subsets Mediated by Parathyroid Hormone and IFN-

Authors

Nathan Young
Natallia Mikhalkevich
Ying Yan
Di Chen
Wei-ping Zeng, Marshall UniversityFollow

Document Type

Article

Publication Date

12-15-2005

Abstract

Bone loss is a typical pathological feature of chronic inflammatory bone diseases including rheumatoid arthritis, in which CD4 effector T cells play critical roles. We found that activated mouse Th2 and not Th1 cells produced the parathyroid hormone (PTH). Unlike in the parathyroid cells, PTH expression in Th2 cells was not regulated by the fluctuation of calcium level, but rather it required the full activation of the T cells. Although PTH was expressed in immature Th2 cells, and its receptor was transiently expressed during Th1 and Th2 cell differentiation, PTH did not significantly affect the outcome of the differentiation. In primary osteoblasts cultured in Th2 cell condition medium, the alkaline phosphatase (ALP) activity was maintained at a basal level. However, antagonizing PTH in the condition medium resulted in a significant reduction of the ALP activity. These results demonstrated an important role of the Th2 cell-derived PTH in maintaining the bone-forming activity of the osteoblasts under inflammatory conditions. In osteoblasts cultured in the Th1 cell condition medium, the ALP activity was significantly suppressed. Neutralizing IFN-γ alleviated the suppression. Conversely, treatment of osteoblasts with IFN-γ suppressed the ALP activity. Unlike ALP, expression of the major bone matrix proteins by the osteoblasts was only minimally affected by either Th1 or Th2 cytokine environment. In addition, the Th2 cytokine environment also regulated to expression of receptor activator of NF-κB ligand and osteoprotegerin through both PTH-dependent and -independent mechanisms. Our study therefore identified new regulatory events in bone remodeling under inflammatory conditions.

Comments

This article first appeared in the December 15, 2005 issue of The Journal of Immunology, the member magazine of the The American Association of Immunologists, and is reprinted with permission.

Copyright © 2005 by The American Association of Immunologists

Recommended Citation

Young, N., N. Mikhalkevich, Y. Yan, D. Chen, W.-p. Zheng. 2005. Differential regulation of osteoblast activity by Th cell subsets mediated by parathyroid hormone and IFN-γ. J. Immunol. 175: 8287-8295.