Expression of RANKL in breast cancer tissue in patients with fibrous dysplasia/McCune-Albright syndrome

Meier, Maartje E.; Hagelstein-Rotman, Marlous; Majoor, B.C.J.; Geels, Raya E.S.; Appelman‐Dijkstra, Natasha M.; Bravenboer, N.

doi:10.1016/j.bone.2023.116679

Cited by 1 publication

(1 citation statement)

References 41 publications

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“…Inflammatory cytokines such as IL-6 have been shown to be produced by the fibrous tissue 45 . However, IL-6 is not elevated in the circulation 46 , and neither IL-6 inhibition nor other anti-inflammatory drugs, decrease significantly bone pain in FD patients 11,47 . Importantly, inflammatory cells are never found within the FD lesion microenvironment, except for mastocytes 48 .…”

Section: Discussionmentioning

confidence: 92%

Bone pain in Fibrous dysplasia does not rely on aberrant sensory nerve sprouting or neuroma formation

Palmisano,

Tavanti,

Farinacci

et al. 2024

Preprint

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Bone pain is a major symptom of many skeletal disorders. Fibrous dysplasia (FD) is a genetic disease with mono or polyostotic skeletal phenotype due to the post-zygotic occurrence of the causative Gsalpha mutation. Bone pain in FD often associates with skeletal deformities and fractures or nerve impingement by the pathological tissue. However, even in the absence of complications, FD patients often complain of a chronic pain that does not correlate with their disease burden. Multiple hypotheses have been made to explain this pain. However, its pathogenetic mechanisms remain, as yet, largely unexplored. In this study, we first demonstrate that the FD mouse model EF1alpha-GsalphaR201C develops a painful-like behavior and an altered response to nociceptive stimuli that, as in FD patients, do not correlate with the severity of their phenotype, thus providing a reliable model to study bone pain in FD. Then, we show that in EF1alpha-GsalphaR201C mice, the overall pattern of skeletal innervation is preserved and that within FD lesions, sensory fibers are variably and focally distributed, mainly at perivascular sites. Finally, we provide the first analysis of a series of human FD bone biopsies showing that sensory nerve fibers are rarely detected within the pathological tissue. These data confirm that bone pain is an intrinsic and reproducible feature of FD. They also show that, albeit sensory nerve fibers are found within FD lesions and may contribute to the unpleasant sensation that accompanies the disease, pathological sensory nerve sprouting or formation of neuromas are not detected in the Gsalpha-mutated skeleton.

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