Inhibition of osteocyte apoptosis by fluid flow is mediated by nitric oxide.
Bone unloading results in osteocyte apoptosis, which attracts osteoclasts leading to bone loss. Loading of bone drives fluid flow over osteocytes which respond by releasing signaling molecules, like nitric oxide (NO), that inhibit osteocyte apoptosis and alter osteoblast and osteoclast activity thereby preventing bone loss. However, which apoptosis-related genes are modulated by loading is unknown. We studied apoptosis-related gene expression in response to pulsating fluid flow (PFF) in osteocytes, osteoblasts, and fibroblasts, and whether this is mediated by loading-induced NO production. PFF (0.7+/-0.3Pa, 5Hz, 1h) upregulated Bcl-2 and downregulated caspase-3 expression in osteocytes. l-NAME attenuated this effect. In osteocytes PFF did not affect p53 and c-Jun, but l-NAME upregulated c-Jun expression. In osteoblasts and fibroblasts PFF upregulated c-Jun, but not Bcl-2, caspase-3, and p53 expression. This suggests that PFF inhibits osteocyte apoptosis via alterations in Bcl-2 and caspase-3 gene expression, which is at least partially regulated by NO.
Tan
S D
SD
Department of Oral Cell Biology, ACTA-Universiteit van Amsterdam and Vrije Universiteit, Research Institute MOVE, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands.
Bakker
A D
AD
Semeins
C M
CM
Kuijpers-Jagtman
A M
AM
Klein-Nulend
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D053148:Caspase 3 / Q000235:genetics; D002642:Chick Embryo; D005786:Gene Expression Regulation; D019254:Genes, bcl-2; D016758:Genes, jun; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011673:Pulsatile Flow; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D053148:Caspase 3; D019331:NG-Nitroarginine Methyl Ester