NOVEL CELL-SURFACE AG EXPRESSED ON RAT OSTEOCLASTS REGULATING THE FUNCTION OF THE CALCITONIN RECEPTOR

Osteoclasts are known to be hematopoietic in origin. However, the deta iled mechanisms of their differentiation and activation are not known. Cell-surface molecules preferentially expressed on cells of the osteo clast lineage may play some important roles in these processes. We pre pared a mAb that recognizes a unique cell-surface membrane protein spe cifically expressed on rat osteoclasts. Expression of this Ag, designa ted as Kat1 Ag, was markedly stimulated by a factor secreted by the os teoblastic cell line ROS 17/2.8. Binding studies of I-125-labeled calc itonin (CT) showed that the Ag was not the CT receptor (CTR). However, interestingly, studies of the biologic activity of this mAb that reco gnizes Kat1-antigen (mAb Kat1) revealed possible regulatory functions of this Ag in osteoclasts. Firstly, mAb Kat1 significantly elevated th e binding affinity of the CTR expressed on osteoclast-like cells witho ut altering the number of receptors. Secondly, CT-sensitivity of the o steoclast 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 inhibit ed osteoclast differentiation in the presence of mAb Kat1, whereas a h igher concentration of CT (10 ng/ml) was required to inhibit their dif ferentiation in the absence of this mAb. Thirdly, mAb Kat1 inhibited d entin-resorbing activity of osteoclast-like cells. Furthermore, the in hibitory effects of CT on osteoclast-mediated dentin resorption was au gmented by the presence of this mAb. These observations strongly sugge st that Kat1-antigen is a unique cell-surface protein regulating the a ffinity of the CTR expressed on osteoclasts and also the bone-resorbin g function of these cells.