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Action of prostaglandins on clonal osteoblastic MC3T3-E1 cells

  • 5. Prostaglandins In Bone Metabolism
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstracts

Prostaglandins (PG's) are well known as an important local regulator of bone metabolism. In this study, we examined to characterize the effects of PGs on osteoblasts, using a clonal osteoblastic MC3T3-E1 cells. Among PG metabolites, PGE2 is a main prostanoid released in bone tissues. MC3T3-E1 cells also produced predominantly PGE2. PG E2 at low doses (1–100 ng/ml) and PGE1 increased activity of alkaline phosphatase (ALP), an marker enzyme of early differentiation of osteoblasts, with positive correlation of elevating intracellular cAMP content. The stimulatory effects are amplified by the addition of isobutylmethyl xanthine (IBMX) and mimicked those of forskolin, a direct activator of adenylate cyclase. those results suggest that PGE2 at low doses and PGE1 act predominantly on adenylate cyclase to stimulate the early differntiation of the cells. On the other hand, PGE2 at high doses (500–2000 ng/ml) and PGF2α stimulated DNA synthesis of the cells in a dose-related manner. In the same range of concentrations, PGE2 and PGF2α augmented the accumulation of inositol triphosphates. Further, the effect of these PGs on the DNA synthesis is negated by addition of H-7, a potent inhibitor of protein kinase C. These date suggest that PGE2 at high doses and PGF2α stimulate the proliferation of the cells via enhance of phosphatidyl inositol (PI) turnover system and following activation of protein kinase C. Since PGE2 reveals diverse effects on the cells dependent on its concentration, it is difficult to clarify the mechanism of PGE2 action. Thus, we chose PGF2α to elucidate the stimulatory effect of PGs on the prolferation of the cells. At least 12h time-lag was present between PG F2α-signal transduction and an increase in DNA synthesis, and α-amanitin and cyclohexamide counteracted the effects, suggesting that some proteins involved in DNA synthesis are produced by the addition of PGF2α in the duration. Further, neutralizing anti IGF-I antibody blocked the stimulation of DNA synthesis by PGF2α. However, PGF2α didn't affect the endogenous production of IGF-I of the cells. On the other hand, PGF2α greatly elevated level of IGF-I binding sites on the cells, and the increase appeared bout 3h earlier than did the stimulation of DNA synthesis, indicating increase in responsiveness of the cells to IGF-I. These results suggest that the proliferation of the cells is stimulated by synergistic action of PGF2α and IGF-I produced endogenously.

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Authors and Affiliations

  1. Department of Oral Anatomy, Meikai University School of Dentistry, 350-02, Sakada, Saitama, Japan

    Yoshiyuki Hakeda, Mamoru Okawa & Masayoshi Kumegawa

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  1. Yoshiyuki Hakeda
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  2. Mamoru Okawa
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  3. Masayoshi Kumegawa
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Hakeda, Y., Okawa, M. & Kumegawa, M. Action of prostaglandins on clonal osteoblastic MC3T3-E1 cells. J Bone Miner Metab 9, 49–56 (1991). https://doi.org/10.1007/BF02377986

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  • DOI: https://doi.org/10.1007/BF02377986

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