Novel cell-surface Ag expressed on rat osteoclasts regulating the function of the calcitonin receptor

Toshio Kukita, Akiko Kukita, Kengo Nagata, Hidefumi Maeda, Kojiro Kurisu, Takeshi Watanabe, Tadahiko Iijima

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Abstract

Osteoclasts are known to be hematopoietic in origin. However, the detailed mechanisms of their differentiation and activation are not known. Cell- surface molecules preferentially expressed on cells of the osteoclast lineage may play some important roles in these processes. We prepared a mAb that recognizes a unique cell-surface membrane protein specifically expressed on rat osteoclasts. Expression of this Ag, designated as Kat1 Ag, was markedly stimulated by a factor secreted by the osteoblastic cell line ROS 17/2.8. Binding studies of 125I-labeled calcitonin (CT) showed that the Ag was not the CT receptor (CTR). However, interestingly, studies of the biologic activity of this mAb that recognizes Kat1-antigen (mAb Kat1) revealed possible regulatory functions of this Ag in osteoclasts. Firstly, mAb Kat1 significantly elevated the binding affinity of the CTR expressed on osteoclast-like cells without altering the number of receptors. Secondly, CT- sensitivity of the osteoclast progenitor cells in the system of osteoclast differentiation showed marked augmentation on treatment of these cells with this mAb. Even a very low concentration of CT (0.1 ng/ml) significantly inhibited osteoclast differentiation in the presence of mAb Kat1, whereas a higher concentration of CT (10 ng/ml) was required to inhibit their differentiation in the absence of this mAb. Thirdly, mAb Kat1 inhibited dentin-resorbing activity of osteoclast-like cells. Furthermore, the inhibitory effects of CT on osteoclast-mediated dentin resorption was augmented by the presence of this mAb. These observations strongly suggest that Kat1-antigen is a unique cell-surface protein regulating the affinity of the CTR expressed on osteoclasts and also the bone-resorbing function of these cells.

Original languageEnglish
Pages (from-to)5265-5273
Number of pages9
JournalJournal of Immunology
Volume153
Issue number11
Publication statusPublished - Dec 1 1994

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Kukita, T., Kukita, A., Nagata, K., Maeda, H., Kurisu, K., Watanabe, T., & Iijima, T. (1994). Novel cell-surface Ag expressed on rat osteoclasts regulating the function of the calcitonin receptor. Journal of Immunology, 153(11), 5265-5273.