• Oursler, Merry Jo (PI)
  • Slavkin, Harold C. (PI)
  • Lipsky, Peter (PI)
  • Slavkin, Harold C. (PI)

Project: Research project

Project Details


In adult life, normal bone metabolism involves a balance between
osteoclast-mediated resorption and osteoblast-mediated formation. This
balance, referred to as coupling, maintains overall bone mass throughout
early adult life. Most diseases relating to the skeletal system, such as
metabolic (osteoporosis, renal osteodystrophy, Paget's, osteoarthritis),
inherited (osteogenesis imperfecta, osteopetrosis), infectious
(periodontal disease) and tumor-based (osteosarcoma, giant cell tumor),
involve abnormalities in the resorption-formation coupling of bone
remodeling. Bone resorption rates are determined by both the number and
activity of osteoclasts. A number of hormonal signals may influence
osteoclast recruitment, differentiation, and/or activity either directly
or indirectly. Clinically, osteoclast dysfunction is a major factor in
postmenopausal osteoporosis. The significant hormonal changes which
begin with the onset of menopause are most likely implicated in
osteoporosis. The principal investigator has recently identified the
presence of estrogen receptor mRNA and functional receptors in isolated
avian osteoclasts and demonstrated direct regulation of osteoclastic bone
resorption. The objective of the proposed studies is to expand the
previously reported direct influence of estrogen on avian
osteoclast-mediated bone resorption to include mammalian estrogen
responses and to identify some of the cellular effectors which mediate
this response. The specific aims of these proposed studies are to: 1)
identify estrogen receptors in avian osteoclasts and human giant cell
tumors, 2) quantitate and characterize the effects of estrogen on avian,
rat and human osteoclast resorptive activity, 3) assess the effects of
estrogen on gene expression of selected osteoclast proteins which have
been implicated in the resorption process, 4) assess the influence of
estrogen on selected osteoclast protein levels and/or activity. Isolated
avian osteoclasts, human osteoclasts and osteoclastomas, and rat
osteoclasts will be challenged with estrogen to study the influence of
steroid hormones on bone resorption. Gene expression influences (mRNA,
protein levels, and enzyme activity) will be examined in avian
osteoclasts and human osteoclastomas in vitro.
Effective start/end date1/1/9312/31/97


  • Medicine(all)