Monocytes mediate osteoclastic bone resorption by prostaglandin production

Jesus H. Dominguez, Gregory R. Mundy

Research output: Contribution to journalArticle

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Abstract

Monocytes are frequently found adjacent to active bone resorption surfaces in both physiological and pathological situations and may play a key role in bone resorption. There is strong circumstantial evidence that monocytes are precursors for osteoclasts in vivo, and recently they have been shown to resorb devitalized bone directly. The present study shows that monocytes can also resorb bone by stimulation of osteoclasts. Live fetal rodent bones prelabeled with45Ca and cultured for 48-96 h in the presence of human monocytes or monocyte-conditioned medium released 80% more mineral than bones cultured in control medium. Bone matrix sustained comparable resorption as demonstrated by a 2-fold decrement in the extracted dry weights of the bones cultured in monocyte-conditioned medium. Histological examination of the bones cultured with monocytes or monocyte-conditioned medium showed increased osteoclast number and activity when compared with bones cultured in control medium. Known inhibitors of osteoclastic activity (phosphate 6 × 10-3M, cortisol 10-6M, and calcitonin 50 mU/ml) inhibited monocyte-conditioned medium-mediated bone resorption. The monocyte-conditioned medium contained sufficient prostaglandin E to account for the bone resorption. Indomethacin 10-5M added to the monocyte cultures blocked monocyte-conditioned media-induced bone resorption and prostaglandin release. These experiments suggest that monocytes stimulate osteoclastic bone resorption by prostaglandin production. Monocyte-induced bone resorption is partly reversed by inhibitors of osteoclast function. Monocyte-induced osteoclastic bone resorption may play an important role in physiologic bone remodeling and in bone destruction that occurs in chronic inflammatory diseases such as rheumatoid arthritis and periodontal disease.

Original languageEnglish (US)
Pages (from-to)29-34
Number of pages6
JournalCalcified Tissue International
Volume31
Issue number1
DOIs
StatePublished - Dec 1 1980

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Keywords

  • Bone resorption
  • Monocytes
  • Osteoclasts
  • Prostaglandins

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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