GLUCOCORTICOID ACTIONS ON OSTEOCLASTS

Project: Research project

Project Details

Description

The chronic inflammatory response which occurs during periodontal disease
often results in tooth loss due to the destruction of alveolar bone.
This destruction is likely, in part, to be the result of osteoclast
stimulation by cytokines produced by the chronic inflammatory cells. In
adult life, normal bone metabolism involves a balance between osteoclast-
mediated resorption and osteoblast-mediated formation. this balance,
referred to as coupling, results in no net change in overall bone
throughout adult life. Most diseases relating to the skeletal system
such as infectious (periodontal disease), metabolic (osteoarthritis,
osteoporosis, renal osteodystrophy, Paget's), inherited (osteogenesis
imperfecta, osteopetrosis), and tumor-based (osteosarcoma, giant cell
tumor), involve abnormalities in the resorption-formation coupling. Bone
resorption rates are determined by both the number and activity level of
osteoclasts. A number of hormonal signals may influence osteoclast
recruitment, differentiation, and/or activity either directly or
indirectly. Clinically, glucocorticoid treatment for rheumatoid
arthritis improves the health of periodontal tissue, but, paradoxically,
treatment often results in glucocorticoid-induced osteoporosis. The
mechanism by which glucocorticoids influence bone metabolism are not well
understood. There are numerous reports of osteoblast responses to
glucocorticoid treatments, but studies on glucocorticoid influences on
bone resorption have shown opposing results. Evidence presented in this
application suggests that highly purified osteoclasts contain
glucocorticoid receptors and that glucocorticoids regulate osteoclast
bone resorption. The objectives of the proposed studies are to verify
the direct influence of glucocorticoids on osteoclast bone resorption and
to identify some of the cellular effectors of this response. The
specific aims of these studies are to: 1) identify and quantitate
glucocorticoid receptors in avian osteoclasts and human giant cell tumors
(osteoclastomas), 2) quantitate and characterize the effect of
glucocorticoids on osteoclast resorption activity, 3) analyze the
influence of glucocorticoids on osteoclast nuclear proto-oncogene
expression and, 4) assess the influence of glucocorticoids on osteoclast
nuclear proto-oncogene expression and, 4) assess the influence of
glucocorticoids on gene expression of selected osteoclast proteins which
have been implicated in the resorption process. Isolated avian
osteoclasts and human osteoclastomas will be used to characterize
osteoclast glucocorticoid receptors. In addition, avian osteoclast and
human osteoclastoma cultures will be challenged with glucocorticoids to
study the influence of glucocorticoids on bone resorption and gene
responses in vitro.
StatusFinished
Effective start/end date7/1/936/30/95

ASJC

  • Medicine(all)
  • Dentistry(all)