Osteocyte biology: its implications for osteoporosis.
Osteocyte viability may play a significant role in the maintenance and integrity of bone. Bone loss due to osteoporosis may be due in part to osteocyte cell death. We have identified a factor that will protect both osteoblasts and osteocytes from cell death due to agents known to be responsible for various forms of osteoporosis. Not only does estrogen preserve osteoblast and osteocyte viability, but so does a molecule called CD40Ligand. This molecule is expressed on activated T lymphocytes, human dendritic cells, and human vascular endothelial cells, whereas its receptor CD40 is expressed on normal epithelium, B cells, and dendritic cells. CD40Ligand protects osteoblasts and the MLO-Y4 osteocyte-like cells against apoptosis induced by glucocorticoids, tumor necrosis factor alpha or etoposide. As tumor necrosis factor a has been shown to be responsible for post-menopausal bone loss and glucocorticoids induce dramatic bone loss, this finding has important implications with regards to potential therapy for both post-menopausal and steroid-induced osteoporosis.
Bonewald
L F
LF
Department of Oral Biology, University of Missouri at Kansas City School of Dentistry, Kansas City, MO 64108-2784, USA. bonewaldl@umkc.edu
D000818:Animals; D017304:Annexin A5 / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects / Q000037:antagonists & inhibitors; D005938:Glucocorticoids / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism*; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D014343:Trypan Blue; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism
D017304:Annexin A5; D004967:Estrogens; D005938:Glucocorticoids; D006133:Growth Substances; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D005047:Etoposide; D014343:Trypan Blue