DNA synthesis is not necessary for osteoclastic responses to parathyroid hormone in cultured fetal rat long bones.

نویسندگان

  • J A Lorenzo
  • L G Raisz
  • J M Hock
چکیده

Osteoclasts, the principal cells mediating bone resorption, are believed to increase their size, number, and resorbing activity in response to parathyroid hormone (PTH) through mechanisms dependent upon the fusion of specific mononuclear precursor cells into either new or existing multinucleated osteoclasts. To address the question of whether these actions of PTH are dependent on the replication of osteoclast precursor cells, we examined the ability of an inhibitor of DNA synthesis, hydroxyurea (HU), to alter bone resorption, osteoclast formation, and DNA synthesis in cultured fetal rat bones treated with PTH. We found that HU significantly reduced [3H]thymidine incorporation into the bones and labeling of osteoclast nuclei by greater than 90%, but did not prevent PTH from stimulating bone resorption, measured as the release of 45Ca, or from increasing the number of osteoclasts in the bones. In bones cultured without PTH, HU decreased the rate of bone resorption, but not the number of osteoclasts per bone. We conclude that in fetal rat bone cultures, PTH can increase osteoclast number and stimulate bone resorption by affecting existing osteoclasts and osteoclast precursors, and that replication of osteoclast precursor cells is not necessary for PTH to stimulate a resorptive response. In unstimulated cultures it appears that HU inhibits bone resorption by affecting mechanisms that are independent of changes in osteoclast number and that may be influenced by cell replication or other unknown factors.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effects of DNA and prostaglandin synthesis inhibitors on the stimulation of bone resorption by epidermal growth factor in fetal rat long-bone cultures.

We examined two inhibitors of DNA synthesis, hydroxyurea (HU) and aphidicholin (APC), and two inhibitors of prostaglandin cyclooxygenase, indomethacin and flufenamic acid, for their effects on the resorptive responses of fetal rat long-bone cultures to epidermal growth factor (EGF) and parathyroid hormone (PTH). As we have previously found, HU decreased unstimulated 45Ca release but had little ...

متن کامل

Carboxyterminal telopeptide of type I collagen, ICTP, as a marker of matrix degradation in neonatal mouse calvarial bones, in vitro.

UNLABELLED Bone resorption, in vitro, is often measured as the release of prelabelled 45Ca from neonatal mouse calvarial bones, or from fetal rat long bones. In this report we describe a technique to measure the breakdown of bone-matrix, in vitro. We also describe a new way to dissect neonatal mouse calvarial bones, in order to obtain large amounts of bone samples. Twelve bone fragments were di...

متن کامل

Effects of endothelial cell growth factor on bone remodelling in vitro.

Endothelial cell growth factor (ECGF) alpha was studied for its effects on bone formation in cultured fetal rat calvariae and on bone resorption in cultured fetal rat long bones. ECGF at 0.1-100 ng/ml stimulated [3H]thymidine incorporation into DNA, an effect enhanced by heparin. Treatment with ECGF for 24 h decreased the incorporation of [3H]proline into collagen but treatment for 48-96 h incr...

متن کامل

Bone cells predispose bone surfaces to resorption by exposure of mineral to osteoclastic contact.

The cell-free endocranial surface of young adult rat parietal bones was used as a substrate for osteoclastic bone resorption, either without prior treatment, or after incubation of the parietal bones with collagenase or neonatal rat calvarial cells. Untreated, the endocranial surface consisted of unmineralized organic fibres; incubation with calvarial cells or collagenase caused disruption and ...

متن کامل

Lymphokine-mediated bone resorption requires endogenous prostaglandin synthesis

Enhanced synthesis of prostaglandin (PG) E by explanted fetal rat bones was initiated by lymphocyte-conditioned media but not by physiological levels of parathyroid hormone. Rapid release of PGE from bone occurred only when the lymphokine was present. Synthesis of PGE preceded and was necessary for the bone resorption caused by the lymphokine preparation. Local production of prostaglandins in r...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of clinical investigation

دوره 72 6  شماره 

صفحات  -

تاریخ انتشار 1983