Exogenous prostacyclin, but not prostaglandin E2, produces similar responses in both G6PD activity and RNA production as mechanical loading, and increases IGF-II release, in adult cancellous bone in culture.
Cyclic mechanical loading in vivo that leads to new bone formation is also associated in osteocytes and surface bone cells with almost immediate increases in G6PD activity, and later increases in RNA production. Both these early, loading-related, responses can be reproduced in organ culture of adult cancellous bone, and both are abolished by the presence of indomethacin in the culture medium at the time of loading. The implication that prostaglandins (PGs) are involved in the control of loading-related osteogenesis is supported by increases in prostacyclin (PGI2) and PGE2 release from cores of cancellous bone during loading. In the experiments reported here, PGE2 and PGI2 were added exogenously (10(-6) M) to perfusable cores of adult canine cancellous bone to determine whether they would simulate the loading-related responses in G6PD activity and RNA synthesis. PGE2 increased G6PD activity in surface cells and osteocytes within 8 minutes but had no effect on [3H]-uridine incorporation at 6 hours. PGI2 stimulated both G6PD activity and [3H]-uridine incorporation equally in osteocytes and surface cells. Neither PG produced any significant change in medium concentrations of IGF-I, and PGE2 had no effect on IGF-II. In contrast PGI2 elevated the medium concentration of IGF-II threefold. IGF-I and IGF-II were localized immunocytochemically to osteocytes and surface cells in both treated and untreated cores. Prostacyclin, but not PGE2, appears to imitate the early loading-related increases in G6PD activity and RNA synthesis in bone cells in situ. Prostacyclin, but not PGE2, also stimulates the early release of IGF-II.
Rawlinson
S C
SC
Department of Veterinary Basic Sciences, Royal Veterinary College, London, England.
Mohan
S
S
Baylink
D J
DJ
Lanyon
L E
LE
D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003470:Culture Media; D015232:Dinoprostone / Q000494:pharmacology*; D004285:Dogs; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D010011:Osteocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010477:Perfusion; D012313:RNA / Q000096:biosynthesis*; D013314:Stress, Mechanical; D014529:Uridine / Q000378:metabolism
D003470:Culture Media; D012313:RNA; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011464:Epoprostenol; D005954:Glucosephosphate Dehydrogenase; D015232:Dinoprostone; D014529:Uridine