|Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
To elucidate the physiology of parathyroid-hormone-related peptide (PTHrP) in chondrocytes, it is essential to investigate on the molecular mechanism of PTHrP receptor mediated signal transduction because PTHrP knock-out mice developed achondroplasia like deformity. In the present projects, we have concentrated in the receptor-mediated signal transduction and PTHrP expression of various cartilage disease. In the former, we have studied the effect of various fragments of PTHrP in primary culture of rat articular chondrocytes and function of the cell lines transfected PTHrP.In the later, we have analyzed the pathophysiological role of parathyroid-hormone-related peptide (PTHrP) in osteoarthritis and rheumatic arthritis.
The action of exogenously added hPTHrP (1-34), hPTHrP (1-141), hPTHrP (100-114) and hPTH (1-34) on thymidine incorporation, alpha (1) type II collagen gene expression, intracellular cAMP and [Ca^<2+>] i level was similar. Antisense oligonucleotides decreased PTHrP mRNA tra
nslation specifically inhibited DNA synthesis. These data are speculated that there is no significant difference among exogenously added hPTH and hPTHrP,on the other hand intracellular PTHrP may have a yet unknown biological role, in addition to a classical PTH/PTHrP receptor-mediated function (J Endocrinology 150 : 359-368 1996).
In tissue regeneration of osteoarthritis and rheumatic arthritis, PTHrP is a key cytokine regulated the cell motility and apoptosis (Br J Rheumatol 35 : 1056-1062 1996, J Osteopaedic Res, in press). To further extend the basic research, we have focused on the critical events of chondrocytes induced by abnormal expression of cytokines escaping from physiological regeneration or apoptosis, which can eventually induce gene instability and abnormal cell proliferation. The experimental design is in vivo rat animal model which was implanted with PTHrP producing osteoblast like cell and developed bone matrix formation around the cells (Endocrine J 43 : 527-535 1996). Furthermore, we have applied the antisense PTHrP oligonucleotide therapy against PTHrP producing tumor (Cancer Res 56 : 77-86,1996).
Finally, we acknowledge a support from this grant and a valuable contribution of our post doc fellows and staffs. Less