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Effects of Prostaglandins on Human Hematopoietic Osteoclast Precursors

INSERM U-349, Hôpital Lariboisiére (S.R., F.P., A.L., C.M., A.J., M.-C.d.V.), Paris, France; and Nuffield Hospital (J.Q.), Oxford, United Kingdom

Address all correspondence and requests for reprints to: M. C. de Vernejoul, M.D., INSERM U-349, Hôpital Lariboisière, 6 rue Guy Patin, 75475 Paris Cedex 10, France.

The effect of prostaglandin E₂ (PGE₂) on osteoclast (OC) differentiation is unclear, either stimulator or inhibitor, depending on the in vitro system used. This probably reflects indirect mechanisms through intermediate cells. We have investigated the direct effect of PGE₂ on human OC differentiation from cord blood monocytes (CBMs) in the absence of stromal cells. Macrophages and multinucleated cells (MNCs) resembling OCs form in cultures of CBMs stimulated by 1,25-dihydroxyvitamin D₃. In the present study, CBMs were cultured for 3 weeks, as previously described, in the presence or absence of PGE₂. The number of MNCs was significantly reduced in the presence of PGE₂ as was the proliferation of cultured CBMs, assessed on day 7. Immunohistochemistry was performed to evaluate macrophage markers (CD11b and CD14) and OC marker (ß₃-chain). PGE₂ significantly increased the numbers of CD11b-positive and CD14-positive cells, whereas the number of ß₃-chain-positive cells was significantly decreased. ß₃-Chain, c-fos, and human calcitonin receptor (h-CTR) messenger RNA (mRNA) expressions were evaluated by reverse transcription-PCR with RNA extracted from cultured CBMs. In the presence of PGE₂, expression of ß₃-chain and c-fos mRNA was reduced from the first week of culture. h-CTR mRNA expression was also reduced, and only the h-CTR1 isoform was detected in the presence of PGE₂. In addition, when PGE₂ was added only during the last week of culture, when no CBM proliferation occurred, the number of CD11b- and ß₃-positive cells was unchanged compared to that in the control culture, as were the proportion of MNCs, the fusion index, and the expression of c-fos mRNA.

In conclusion, our results suggest that PGE₂ has an inhibitory effect on human OC differentiation from CBMs, possibly by reducing precursor proliferation in these cultures. We also hypothesize that PGE₂ may reduce OC differentiation by increasing the proportion of precursor cells that differentiate into macrophages. In addition, this may be the result of inhibition of the c-fos expression in CBMs.

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