Mechanical strain-induced NO production by bone cells: a possible role in adaptive bone (re)modeling?
The structural competence of the skeleton is maintained by an adaptive mechanism in which resident bone cells respond to load-induced strains. To investigate the possible role of the messenger molecule nitric oxide (NO) in this response, we studied NO production in well-characterized organ culture systems, rat long bone-derived osteoblast-like (LOBs) cells, and embryonic chick osteocytes (LOCYs) in monolayer culture. In superfused cancellous bone cores, loading (for 15 min) produces increases in NO2- (stable NO metabolite) release during the loading period, which paralleled those in PGI2 and PGE2. Loading of rat vertebrae and ulnae produces increases in NO2- release, and in ulnae NO synthase inhibitors diminish these responses. Transient rapid increases in NO release are stimulated by strain in both LOBs and LOCYs. Polymerase chain reaction amplification of extracted mRNA shows that rat ulnae, LOBs, and LOCYs express both the inducible and neuronal (constitutive) isoforms of NO synthase. Adaptability to mechanical strain relies on assessment of the strain environment followed by modification of bone architecture. Immediate increases in NO production induced by loading suggest the involvement of NO in strain measurement and cellular communication to establish strain distribution, as well as potentially in adaptive changes in bone cell behavior.
Pitsillides
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AA
Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, United Kingdom.
Rawlinson
S C
SC
Suswillo
R F
RF
Bourrin
S
S
Zaman
G
G
Lanyon
L E
LE
D000222:Adaptation, Physiological; D000818:Animals; D001483:Base Sequence; D016723:Bone Remodeling / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004285:Dogs; D004790:Enzyme Induction; D005260:Female; D005269:Femur / Q000166:cytology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000166:cytology; D013314:Stress, Mechanical; D014457:Ulna / Q000166:cytology
D007527:Isoenzymes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase