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The role of osteoblast cells in the pathogenesis of unicameral bone cysts

The role of osteoblast cells in the pathogenesis of unicameral bone cysts
The role of osteoblast cells in the pathogenesis of unicameral bone cysts
Purpose
The pathogenesis of unicameral bone cysts (UBCs) remains largely unknown. Osteoclasts have been implicated, but the role of osteoblastic cells has, to date, not been explored. This study investigated the pathophysiology of UBCs by examining the interactions between the cyst fluid and human bone marrow stromal cells (hBMSCs) and the effect of the fluid on osteogenesis.

Methods
Fluid was aspirated from two UBCs and analysed for protein, electrolyte and cytokine levels. Graded concentrations of the fluid were used as culture media for hBMSCs to determine the effects of the fluid on hBMSC proliferation and osteogenic differentiation. The fibrocellular lining was analysed histologically and by electron microscopy.

Results
Alkaline phosphatase (ALP) staining of hBMSCs that were cultured in cyst fluid demonstrated increased cell proliferation and osteogenic differentiation compared to basal media controls. Biochemical analysis of these hBMSCs compared to basal controls confirmed a marked increase in DNA content (as a marker of proliferation) and ALP activity (as a marker of osteogenic differentiation) which was highly significant (p < 0.001). Osteoclasts were demonstrated in abundance in the cyst lining. The cyst fluid cytokine profile revealed levels of the pro-osteoclast cytokines IL-6, MIP-1? and MCP-1 that were 19×, 31× and 35× greater than those in reference serum.

Conclusions
Cyst fluid promoted osteoblastic growth and differentiation. Despite appearing paradoxical that the cyst fluid promoted osteogenesis, osteoblastic cells are required for osteoclastogenesis through RANKL signalling. Three key cytokines in this pathway (IL-6, MIP-1?, MCP-1) were highly elevated in cyst fluid. These findings may hold the key to the pathogenesis of UBCs, with implications for treatment methods.
1863-2521
339-346
Aarvold, Alexander
11dc317f-47fd-4b2c-b0a6-78688c679b5a
Smith, James O.
027f2a5a-1966-4077-97a7-f70d2e6b06b2
Tayton, Edward R
96db2df6-e8ca-4709-a13d-16b8f05aff5c
Edwards, Caroline J.
3f551918-eefb-436e-a198-0930f77c8b4e
Fowler, Darren J.
1a27c8b0-21bf-48d0-aef3-8aedd3ee1f6f
Gent, Edward D.
8c77379a-cf23-4d30-a1ba-0f94303255e9
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Aarvold, Alexander
11dc317f-47fd-4b2c-b0a6-78688c679b5a
Smith, James O.
027f2a5a-1966-4077-97a7-f70d2e6b06b2
Tayton, Edward R
96db2df6-e8ca-4709-a13d-16b8f05aff5c
Edwards, Caroline J.
3f551918-eefb-436e-a198-0930f77c8b4e
Fowler, Darren J.
1a27c8b0-21bf-48d0-aef3-8aedd3ee1f6f
Gent, Edward D.
8c77379a-cf23-4d30-a1ba-0f94303255e9
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778

Aarvold, Alexander, Smith, James O., Tayton, Edward R, Edwards, Caroline J., Fowler, Darren J., Gent, Edward D. and Oreffo, Richard O.C. (2012) The role of osteoblast cells in the pathogenesis of unicameral bone cysts. Journal of Children's Orthopaedics, 6 (4), 339-346. (doi:10.1007/s11832-012-0419-x). (PMID:23904902)

Record type: Article

Abstract

Purpose
The pathogenesis of unicameral bone cysts (UBCs) remains largely unknown. Osteoclasts have been implicated, but the role of osteoblastic cells has, to date, not been explored. This study investigated the pathophysiology of UBCs by examining the interactions between the cyst fluid and human bone marrow stromal cells (hBMSCs) and the effect of the fluid on osteogenesis.

Methods
Fluid was aspirated from two UBCs and analysed for protein, electrolyte and cytokine levels. Graded concentrations of the fluid were used as culture media for hBMSCs to determine the effects of the fluid on hBMSC proliferation and osteogenic differentiation. The fibrocellular lining was analysed histologically and by electron microscopy.

Results
Alkaline phosphatase (ALP) staining of hBMSCs that were cultured in cyst fluid demonstrated increased cell proliferation and osteogenic differentiation compared to basal media controls. Biochemical analysis of these hBMSCs compared to basal controls confirmed a marked increase in DNA content (as a marker of proliferation) and ALP activity (as a marker of osteogenic differentiation) which was highly significant (p < 0.001). Osteoclasts were demonstrated in abundance in the cyst lining. The cyst fluid cytokine profile revealed levels of the pro-osteoclast cytokines IL-6, MIP-1? and MCP-1 that were 19×, 31× and 35× greater than those in reference serum.

Conclusions
Cyst fluid promoted osteoblastic growth and differentiation. Despite appearing paradoxical that the cyst fluid promoted osteogenesis, osteoblastic cells are required for osteoclastogenesis through RANKL signalling. Three key cytokines in this pathway (IL-6, MIP-1?, MCP-1) were highly elevated in cyst fluid. These findings may hold the key to the pathogenesis of UBCs, with implications for treatment methods.

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Published date: 2012
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 355842
URI: https://eprints.soton.ac.uk/id/eprint/355842
ISSN: 1863-2521
PURE UUID: a9fb603d-bd94-4360-a41b-75c7a31d5c68
ORCID for Richard O.C. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

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Date deposited: 02 Jan 2014 11:33
Last modified: 06 Jun 2018 12:53

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