Gallium nitrate inhibits bone resorption and collagen synthesis in neonatal mouse calvariae

Peter Lakatos, Seymour Mong, Paula H. Stern

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Gallium nitrate (GN) is an agent used in the treatment of hypercalcemia. To more fully characterize the direct actions of GN on bone, we examined its effects on medium calcium, medium β‐glucuronidase (β‐GLU), and collagen synthesis in control and hormone‐stimulated neonatal (4–6 days) mouse calvariae in vitro. GN (10 μg/ml) inhibited parathyroid hormone‐stimulated (PTH; 1 nM) calcium release. A 24 h preincubation with 10 μg/ml of GN was required for complete inhibition; partial inhibition was seen with 12 h preincubation; 1, 3, or 6 h was inadequate. A dose‐response study showed that with 24 h preincubation, 5, 3, and 1 μg/ml of GN inhibited 81, 62, and 0% of PTH‐induced calcium release. The effects of GN on the release of β‐GLU generally paralleled those on the release of calcium except that 10 μg/ml of GN stimulated β‐GLU release. Collagen synthesis was inhibited 50% by 3 μg/ml of GN, whereas noncollagen protein synthesis was unaffected. With PTH + GN no further decrease was observed. When GN was withdrawn from the medium after 24 h of preincubation, the inhibitory effect on calcium release and β‐GLU activity, but not on collagen synthesis, persisted through the 72 h of culture. GN also inhibited the resorption elicited by thyroxine (1 μM) and interleukin‐1β (10 nM) but not by 1,25‐dihydroxyvitamin D3 (30 pM). Our results indicate that GN is a powerful inhibitor of bone resorption in neonatal mouse calvariae even at low doses. A preexposure time is required to induce the persistent effect, but the continuous presence of GN is not necessary to maintain its effects on bone. Although GN has a primary cellular site of action, the requirement for preculture could suggest that GN could, in addition, make the bone matrix more resistant to resorption.

Original languageEnglish
Pages (from-to)1121-1126
Number of pages6
JournalJournal of Bone and Mineral Research
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 1991

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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