Involvement of different ion channels in osteoblasts' and osteocytes' early responses to mechanical strain.
The involvement of functional ion channels in previously documented early responses of osteocytes and osteoblasts to mechanical strain in bone tissue was investigated in explants of rat ulnae by the use of ion channel blockers. Gadolinium chloride (a blocker of stretch/shear-sensitive cation channels) elevated basal prostaglandin (PG) E2 and prostacyclin (PGI2) release and osteocyte glucose-6-phosphate dehydrogenase (G6PD) activity, but was associated with a reduction in basal nitric oxide (NO) production. Gadolinium abolished loading-related increases in the release of PGI2 and NO and osteocyte G6PD activity. Gadolinium also reduced the loading-related release of PGE2 assumed to originate from osteoblasts and the magnitude of loading-related increases in G6PD activity in these cells. Nifedipine (a blocker of L-type voltage-dependent calcium channels) had no effect on basal levels of prostanoid or NO release, or G6PD activity in osteocytes or osteoblasts, and did not affect loading-related release of PGI2 or increase in osteocyte G6PD. However, nifedipine prevented loading-related increases in PGE2 and NO release and osteoblast G6PD activity. These results are consistent with osteocytes' response to bone loading requiring activatable ion channels sensitive to gadolinium, but not those sensitive to nifedipine. In osteoblasts, the early responses to bone loading appear to be associated with ion channels sensitive to gadolinium and nifedipine; however, the nifedipine-sensitive channels seem to have the dominant effect.
Rawlinson
S C
SC
Department of Veterinary Basic Sciences, The Royal Veterinary College, London, UK.
Pitsillides
A A
AA
Lanyon
L E
LE
D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000166:cytology* / Q000502:physiology; D011464:Epoprostenol / Q000378:metabolism; D005682:Gadolinium / Q000008:administration & dosage; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010011:Osteocytes / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical; D014457:Ulna / Q000166:cytology / Q000502:physiology
D007473:Ion Channels; D011453:Prostaglandins; D009569:Nitric Oxide; D005682:Gadolinium; D011464:Epoprostenol; D005954:Glucosephosphate Dehydrogenase; D009543:Nifedipine