Effect of prostaglandins E1, E2, and F2α on osteoclast formation in mouse bone marrow cultures

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Abstract
Prostaglandins (PG) act as direct inhibitors of mature osteoclasts, but although resorption‐inhibition is also observed initially PG increase bone resorption in organ culture. This suggests that PG influence bone resorption in organ culture through actions on cell types other than mature osteoclasts. We have therefore tested the effects of PG E1, E2, and F2α on the differentiation of osteoclastic phenotype in mouse bone marrow cultures using bone resorption and calcitonin receptors (CTR) as markers of osteoclastic differentiation. We found that PGE2 (10−6–10−9 M) and PGE1 (10−6–10−7 M) induced a significant increase in CTR‐positive cell numbers, to levels five to eight times those seen in controls and similar to the number induced by 1,25‐dihydroxyvitamin D3 [1,25‐(OH)2D3]. Bone resorption was increased (10−7 M PGE2 and 10−6 M PGE1) in association with the increased CTR‐positive cell numbers, suggesting that the PG also induced resorptive function. 1,25‐(OH)2D3 increased both the number of CTR‐positive cells and the extent of resorption per cell; the additional presence of PG did not affect the number of CTR‐positive cells but did reduce bone resorption compared with 1,25‐(OH)2D3 alone. PGF2α had no significant effect on CTR‐positive cell induction or bone resorption. The results suggest that PGE1 and E2 induce osteoclastic differentiation in mouse bone marrow cultures and inhibit the function of the osteoclasts thus formed. The explanation for this apparently paradoxical behavior may be that osteoclast generation occurs in a different microenvironment from that in which osteoclast function is regulated and that PG production may be inversely modulated at the two sites, in response to a given stimulus, to effect a change in bone resorption.
Funding Information
  • Arthritis and Rheumatism Council and Cancer Research Campaign

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