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

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-1a and MCP-1 that were 199, 319 and 359 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-1a, MCP-1) were highly elevated in cyst fluid. These findings may hold the key to the pathogenesis of UBCs, with implications for treatment methods.

An unusual case of proximal humeral simple bone cyst in an adult from secondary cystic change

“…With biochemical analyses of SBC fluid having demonstrated increased levels of PGE2 [ 8 , 36 ], IL-1 [ 36 ], proteolytic enzymes [ 7 , 36 ], and acid phosphatase [ 37 ], we can now possibly link trauma-induced inflammation with SBC developing from an increased osteoclast activity. Having demonstrated the promotion of osteoblastic growth and differentiation with SBC fluid, Aarvold et al proposed a receptor activator of nuclear factor kappa-B ligand (RANKL) signaling mechanism for the osteoclastogenesis [ 38 ], supporting an earlier study observing direct interaction between osteoclast progenitors and osteoblastic cells in the osteoclast recruitment induced by IL-1 [ 34 ].…”

Elastic intramedullary nailing combined with methylprednisolone acetate injection for treatment of unicameral bone cysts in children: A retrospective study

“…Several factors may be involved: i) epiphyseal plate injury leading to disorder of osteogenesis function; 13,16 ii) Interleukin 1 beta, PGE2, oxygen free radicals and lysosomes in the cyst fluid destroying bone tissue; and iii) pressure build-up in the cyst due to venous obstruction in the bone, destroying bone tissue. 1,10,17 Because the aetiology is not completely elucidated, surgery performed on the basis of one theory might result in a recurrence. Steroid injection and autologous bone marrow injections aim at inducing the differentiation of the osteogenesis.…”

“…9 To date, there have been many theories and no consensus on the pathogenesis of UBCs. 10 Among the theories, two are widely accepted by most surgeons. The first is blocked fluid drainage causing pressure changes; therefore, the treatment method is to destroy the local venous obstruction by aspiration, curettage, screw-assisted continuous drainage, elastic intramedullary nailing (EIN) or intra-drainage.…”

Doxycycline Injection Treatment for Unicameral Bone Cysts: a Case Series

“…(18) One of the hallmarks of UBC histopathology is abundant osteoclasts in the lining tissue suggesting that RANKL may play a critical role in local osteoclast recruitment and activation similar to what is observed in ABCs. (19,20) Doxycycline is also a calcium chelator thereby interfering with bone remodeling. (21) Therefore, it is likely that doxycycline works through multiple mechanisms to reverse UBC-mediated osteolysis.…”