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. 2012 Aug;6(4):339-46.
doi: 10.1007/s11832-012-0419-x. Epub 2012 Jul 7.

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

Alexander Aarvold  1 , James O Smith, Edward R Tayton, Caroline J Edwards, Darren J Fowler, Edward D Gent, Richard O C Oreffo
Affiliations

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

Alexander Aarvold et al. J Child Orthop. 2012 Aug.

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-1α 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-1α, MCP-1) were highly elevated in cyst fluid. These findings may hold the key to the pathogenesis of UBCs, with implications for treatment methods.

Keywords: Cytokine; Osteoblast cell; Osteoclast; RANK ligand; Unicameral bone cyst.

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Figures

Fig. 1
Fig. 1
Radiographs of UBCs from cases 1 and 2: preoperative AP and lateral radiographs of case 1 (a, b proximal femur) and case 2 (e, f proximal humerus). Intraoperative fluoroscopy of percutaneous aspiration and cystogram, followed by stabilisation with flexible nailing, of case 1 (c, d) and case 2 (g, h)
Fig. 2
Fig. 2
Photomicroscope images of ALP-stained hBMSC cultures in graded cyst fluid concentrations [0 % (a, d), 25 % (b, e), 50 % (c, f)] showed increased cell proliferation and ALP staining with increased cyst fluid concentrations. Scale bars 200 μm
Fig. 3
Fig. 3
Biochemical assays of hBMSCs cultured with graded concentrations of cyst fluid from cyst 1 (left column) and cyst 2 (right column). Error bars denote the standard deviation, ***p < 0.001. Each assay was run in triplicate
Fig. 4
Fig. 4
Electron micrograph (EM) and histological section of the fibrocellular lining of the UBC. a EM demonstrated large osteoclast-like cells with multiple nuclei (arrows). b Histological images of the cyst wall revealed multiple osteoclasts in the paratrabecular region (arrows)
Fig. 5
Fig. 5
Flow chart of the RANKL signalling pathway, illustrating the dependence of osteoclasts on osteoblasts for their function, and the role of MCP-1, MIP-1α and IL-6
See this image and copyright information in PMC

References

    1. Capanna R, Campanacci DA, Manfrini M. Unicameral and aneurysmal bone cysts. Orthop Clin North Am. 1996;27(3):605–614. - PubMed
    1. Cohen J. Simple bone cysts. Studies of cyst fluid in six cases with a theory of pathogenesis. J Bone Joint Surg Am. 1960;42-A:609–616. - PubMed
    1. Komiya S, Kawabata R, Zenmyo M, Hashimoto S, Inoue A. Increased concentrations of nitrate and nitrite in the cyst fluid suggesting increased nitric oxide synthesis in solitary bone cysts. J Orthop Res. 2000;18(2):281–288. doi: 10.1002/jor.1100180217. - DOI - PubMed
    1. Chigira M, Maehara S, Arita S, Udagawa E. The aetiology and treatment of simple bone cysts. J Bone Joint Surg Br. 1983;65(5):633–637. - PubMed
    1. Gerasimov AM, Toporova SM, Furtseva LN, Berezhnoy AP, Vilensky EV, Alekseeva RI. The role of lysosomes in the pathogenesis of unicameral bone cysts. Clin Orthop Relat Res. 1991;266:53–63. - PubMed