Advances in Models of Fibrous Dysplasia/McCune-Albright Syndrome

Lung, Hsuan; Hsiao, Edward C.; Wentworth, Kelly

doi:10.3389/fendo.2019.00925

Cited by 15 publications

(18 citation statements)

References 37 publications

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“… 8 In contrast, the expression of the mutation in early progenitor cells residing within the bone marrow stroma leads to a dramatic derangement of bone and marrow architecture and function. 7 , 9 These results are consistent with current knowledge of the biology and activity of bone marrow osteoprogenitor cells. However, the bone marrow stromal cell (BMSC) system is heterogeneous and comprises not only osteoprogenitor cells but also contains progenitors committed to the adipogenic lineage.…”

Section: Introductionsupporting

confidence: 87%

“…However, significant insights were provided by transgenic mice in which a gain of function mutation of Gsα was expressed in a ubiquitous and constitutive manner, 7 or at specific differentiation stages of maturation within the osteogenic lineage. 8 , 9 Overall, these models demonstrated that dysregulated activity of Gsα in differentiated osteoblasts stimulates bone formation but does not affect the bone marrow microenvironment. 8 In contrast, the expression of the mutation in early progenitor cells residing within the bone marrow stroma leads to a dramatic derangement of bone and marrow architecture and function.…”

Section: Introductionmentioning

confidence: 85%

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GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

et al. 2022

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The Gsα/cAMP signaling pathway mediates the effect of a variety of hormones and factors that regulate the homeostasis of the post-natal skeleton. Hence, the dysregulated activity of Gsα due to gain-of-function mutations (R201C/R201H) results in severe architectural and functional derangements of the entire bone/bone marrow organ. While the consequences of gain-of-function mutations of Gsα have been extensively investigated in osteoblasts and in bone marrow osteoprogenitor cells at various differentiation stages, their effect in adipogenically-committed bone marrow stromal cells has remained unaddressed. We generated a mouse model with expression of GsαR201C driven by the Adiponectin (Adq) promoter. Adq-GsαR201C mice developed a complex combination of metaphyseal, diaphyseal and cortical bone changes. In the metaphysis, GsαR201C caused an early phase of bone resorption followed by bone deposition. Metaphyseal bone formation was sustained by cells that were traced by Adq-Cre and eventually resulted in a high trabecular bone mass phenotype. In the diaphysis, GsαR201C, in combination with estrogen, triggered the osteogenic activity of Adq-Cre-targeted perivascular bone marrow stromal cells leading to intramedullary bone formation. Finally, consistent with the previously unnoticed presence of Adq-Cre-marked pericytes in intraosseous blood vessels, GsαR201C caused the development of a lytic phenotype that affected both cortical (increased porosity) and trabecular (tunneling resorption) bone. These results provide the first evidence that the Adq-cell network in the skeleton not only regulates bone resorption but also contributes to bone formation, and that the Gsα/cAMP pathway is a major modulator of both functions.

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Section: Introductionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 85%

GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

et al. 2022

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“…embryonic stage (22). The mutated GNAS gene to the activation of the TSH/G protein pathway and the subsequent elevated intracellular adenosine 3',5'-cyclic monophosphate level (23,24). Interestingly, for patients who had the typical triad, mutations of the GNAS gene were detected in 46% of the peripheral blood samples of the patients, while in patients with two or one symptom, this number dropped to 21% and 8%, respectively (25).…”

Section: Figurementioning

confidence: 99%

Case report: Surgical treatment of McCune-Albright syndrome with hyperthyroidism and retrosternal goiter: A case report and literature review

et al. 2023

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IntroductionMcCune-Albright syndrome (MAS) is a low-incidence syndrome consisting of the clinical triad of fibrous structural dysplasia of bone, endocrine disease, and skin pigmentation. Thyroid dysfunction is the second most common endocrine dysregulation in MAS. However, there are no treatment guidelines for MAS complicated with hyperthyroidism. Notably, no case of MAS complicated with retrosternal goiter and hyperthyroidism has been reported to our knowledge.Case presentationWe report a 27-year-old man with MAS who developed the typical triad of bone fibrous dysplasia, skin pigmentation and hyperthyroidism, complaining of recent fast-growing neck mass and difficulty in breathing. Hyperthyrodism was under control by Thiamazole, and computed tomography showed an enlarged thyroid extending retrosternally. We performed a total thyroidectomy on the patient. At the 1-year follow-up, the patient's dyspnea, hyperthyroidism, and bone pain were all significantly alleviated.ReviewWe searched the literature for previous case reports concerning MAS patients complicated with thyroid dysregulation. A total of 17 articles and 22 patients were identified to form our database. Among them, 9 studies clearly mentioned surgical intervention in 11 patients, and prognoses were also reported. Surgery was the most common intervention chosen and indicated a satisfactory prognosis.ConclusionWe report a rare case of MAS patient complicated with retrosternal goiter and hyperthyroidism. Our review provides an overview of MAS cases requiring interventions on thyroid function, and total thyroidectomy should be a proper treatment for these patients.

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“…In MAS there is an increased activity of Gs protein signaling, caused by an acquired somatic gain-of-function mutation in the GNAS gene encoding its alpha subunit. G protein coupled receptors (GPCRs) participate in multiple cellular pathways, including some that have been identified as regulators of osteoblast formation and function, influencing bone formation and homeostasis [2,3]. The most accepted models and theories affirm that the mutation is postzygotic, explaining the mosaicism that characterizes the disease, also justified by the ubiquity of the protein in the affected tissues, making the range of extension and severity of its manifestation variable [2,3].…”

Section: Etiology and Pathophysiologymentioning

confidence: 99%

Mccune Albright Syndrome/Craniofacial Fibrous Dysplasia and Postcraniectomy Syndrome: Case Report and Literature Review

Rodríguez¹

2022

Arch Clin Trial & Case Rep.

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Introduction: McCune Albright syndrome (MAS) is a rare pathology caused by a genetic mutation of the GNAS1 gene that causes fibrous dysplasia (FD) among other endocrinological and metabolic manifestations (1). Here is presented a case report, in which craniofacial dysplasia (CFFD) produces functional alteration, its treatment, and the management of underlying complications. Case report: A 10-year-old female patient who presented with CFD with progressive involvement of the orbital cavity, compression of the optic nerve and right oculomotor cranial nerves, associated with precocious puberty and the appearance of ‘’café-au-lait’’ spots on the skin and finally, the diagnosis of MAS is made. Right front-parieto-temporal craniectomy and intracanalicular decompression of the optic nerve was performed getting partial improvement of functional alteration. Subsequently, cranioplasty is performed to manage postcraniectomy/trephined syndrome. Discussion: MAS is a genetic postzygotic disease that occurs in early stages of embryonic development, which explains its mosaicism. Among its manifestation is FD, which is explained by the hyperfunctioning nature of the mutation. In the case of DCF, continuous surveillance is required by a multidisciplinary team that includes a neurosurgeon, whose intervention is reserved for cases in which functional alterations occur, following the recommendations given by medical literature regarding the approach and type of surgery. Decompressive craniectomy can be associated with complications such as postcraniectomy/trephined syndrome, which shows improvement or resolution with cranioplasty. Conclusion: The diagnosis of MAS is clinical, and its mosaicism is explained by its early presentation in embryonic development. In the case of FCD with functional compromise, neurosurgical intervention is required, seeking the recovery and preservation of the compromised cranial nerves, avoiding prophylactic decompressions. In case of complications such as postcraniectomy/trephination syndrome, timely cranioplasty should be performed as it turns out to be highly effective as a treatment, however, the need for studies aimed at its characterization and diagnosis arises.

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Advances in Models of Fibrous Dysplasia/McCune-Albright Syndrome

Cited by 15 publications

References 37 publications

GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

Case report: Surgical treatment of McCune-Albright syndrome with hyperthyroidism and retrosternal goiter: A case report and literature review

Mccune Albright Syndrome/Craniofacial Fibrous Dysplasia and Postcraniectomy Syndrome: Case Report and Literature Review

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