[Effects of protease inhibitors and protein synthesis inhibitors on cartilage tissue-dependent bone resorption].
We studied bone resorption of fetal rat femora in association with cartilage tissue. Some protease inhibitors, e.g., E-64, pepstatin A, phosphoramidon, amastatin, bestatin, foroxymithine, did not influence the bone resorption, but some serine protease inhibitors such as PMSF, TLCK, TPCK and elastatinal inhibited the bone resorption at 10(-5) M, 10(-4) M, 10(-4) M, 10(-4) M, respectively. A conditioned medium, obtained from cartilage tissue-cultured medium in the presence of 10(-4) M TPCK, which was then excluded from the medium by dialysis after the culture, stimulated the bone resorption. Cycloheximide (0.1 to 10 micrograms/ml) and puromycin (0.3 to 30 micrograms/ml) inhibited the cartilage tissue-dependent bone resorption. A A transient treatment of the femora with cycloheximide (3 micrograms/ml) for a day inhibited the bone resorption, but after the treatment, in the absence of cycloheximide, the femora gradually recovered the bone-resorbing activity. The conditioned medium, obtained from cartilage tissue-cultured medium in the presence of cycloheximide (3 micrograms/ml), which was then excluded from the medium by dialysis after the culture, failed to influence the bone resorption. These findings collectively suggest that cartilage tissue produces a bone resorption-stimulating factor(s) which is a serine protease or contains the protein as an inactive, latent form and then a certain serine protease converts it to an active form.
Tsutsumi
N
N
Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
Nagata
H
H
Arai
N
N
Kojima
M
M
Ujiie
A
A
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D002356:Cartilage / Q000737:chemistry / Q000502:physiology*; D046508:Culture Techniques; D005260:Female; D005333:Fetus; D011480:Protease Inhibitors / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D011480:Protease Inhibitors; D011500:Protein Synthesis Inhibitors