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Inhibition of bone resorption by inorganic phosphate is mediated by both reduced osteoclast formation and decreased activity of mature osteoclasts

Inhibition of bone resorption by inorganic phosphate is mediated by both reduced osteoclast formation and decreased activity of mature osteoclasts
Inhibition of bone resorption by inorganic phosphate is mediated by both reduced osteoclast formation and decreased activity of mature osteoclasts
High concentrations of inorganic phosphate (Pi) are known to inhibit bone resorption, although the mechanism(s) underlying this effect is unclear. To investigate whether Pi can inhibit the formation of osteoclasts we studied the effects of changes in Pi concentration between 1 and 4 mM on osteoclast-like cell formation in 1 week cultures of mouse bone marrow. Osteoclast-like cells were identified by multinuclearity, positive staining for tartrate-resistant acid phosphatase (TRAP), and contraction in response to calcitonin. Increasing concentrations of Pi inhibited formation of these cells in a dose-dependent manner. To study effects of Pi on the bone-resorbing activity of mature osteoclasts we isolated osteoclasts from calcium-deficient egg-laying hens or rat pups and incubated them on sperm whale dentine slices. High Pi concentrations markedly reduced both the number of resorption pits formed per dentine slice and the mean area of each pit in both avian and mammalian systems. These data indicate that high concentrations of Pi act on bone directly, both to inhibit generation of new osteoclasts from their precursor cells and to inhibit bone resorption by mature osteoclasts. These effects of extracellular Pi concentration may play an important modulatory role on bone turnover in vivo and have potential importance in several disease states in which Pi metabolism is perturbed.
0884-0431
473-478
Yates, A.J.
9a885b24-fc47-4361-bd4a-8075368c84a0
Oreffo, R.O.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Mayor, K.
3a3a3b6c-fa2e-4ba1-8d75-0dd43acfedfd
Mundy, G.R.
921d7037-eb6c-48bb-97a0-52d2647ccfda
Yates, A.J.
9a885b24-fc47-4361-bd4a-8075368c84a0
Oreffo, R.O.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Mayor, K.
3a3a3b6c-fa2e-4ba1-8d75-0dd43acfedfd
Mundy, G.R.
921d7037-eb6c-48bb-97a0-52d2647ccfda

Yates, A.J., Oreffo, R.O., Mayor, K. and Mundy, G.R. (1991) Inhibition of bone resorption by inorganic phosphate is mediated by both reduced osteoclast formation and decreased activity of mature osteoclasts. Journal of Bone and Mineral Research, 6 (5), 473-478. (doi:10.1002/jbmr.5650060508). (PMID:2068953)

Record type: Article

Abstract

High concentrations of inorganic phosphate (Pi) are known to inhibit bone resorption, although the mechanism(s) underlying this effect is unclear. To investigate whether Pi can inhibit the formation of osteoclasts we studied the effects of changes in Pi concentration between 1 and 4 mM on osteoclast-like cell formation in 1 week cultures of mouse bone marrow. Osteoclast-like cells were identified by multinuclearity, positive staining for tartrate-resistant acid phosphatase (TRAP), and contraction in response to calcitonin. Increasing concentrations of Pi inhibited formation of these cells in a dose-dependent manner. To study effects of Pi on the bone-resorbing activity of mature osteoclasts we isolated osteoclasts from calcium-deficient egg-laying hens or rat pups and incubated them on sperm whale dentine slices. High Pi concentrations markedly reduced both the number of resorption pits formed per dentine slice and the mean area of each pit in both avian and mammalian systems. These data indicate that high concentrations of Pi act on bone directly, both to inhibit generation of new osteoclasts from their precursor cells and to inhibit bone resorption by mature osteoclasts. These effects of extracellular Pi concentration may play an important modulatory role on bone turnover in vivo and have potential importance in several disease states in which Pi metabolism is perturbed.

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Published date: May 1991
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 360853
URI: http://eprints.soton.ac.uk/id/eprint/360853
ISSN: 0884-0431
PURE UUID: 6e0d05bf-106c-4af5-8df7-2cdef06b49b6
ORCID for R.O. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

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Date deposited: 08 Jan 2014 16:40
Last modified: 15 Mar 2024 03:04

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Contributors

Author: A.J. Yates
Author: R.O. Oreffo ORCID iD
Author: K. Mayor
Author: G.R. Mundy

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