Bone resorption in syndromes of the Ras/MAPK pathway

Da Stevenson, El Schwarz, Jc Carey, Dh Viskochil, H. Hanson, S. Bauer, H. Y. Cindy Weng, T. Greene, K. Reinker, J. Swensen, Rebecca Chan, F. C. Yang, L. Senbanjo, Z. Yang, R. Mao, M. Pasquali

Research output: Contribution to journalArticle

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Abstract

Disorders of the Ras/mitogen-activated protein kinase (MAPK) pathway have an overlapping skeletal phenotype (e.g. scoliosis, osteopenia). The Ras proteins regulate cell proliferation and differentiation and neurofibromatosis type 1 (NF1) individuals have osteoclast hyperactivity and increased bone resorption as measured by urine pyridinium crosslinks [pyridinoline (Pyd) and deoxypyridinoline (Dpd)]. Pyd and Dpd are hydroxylysine-derived crosslinks of collagen found in bone and cartilage and excreted in the urine. Dpd is most abundant in bone. The aim of this study was to evaluate if other syndromes of the Ras/MAPK pathway have increased bone resorption, which may impact the skeletal phenotype. Participants were individuals with Noonan syndrome (n = 14), Costello syndrome (n = 21), and cardiofaciocutaneous (CFC) syndrome (n = 14). Pyridinium crosslinks from two consecutive first morning urines were extracted after acid hydrolysis and analyzed by high performance liquid chromatography. Three separate analyses of covariance were performed to compare Pyd, Dpd, and Dpd/Pyd ratio of each group to controls after controlling for age. Data were compared to 99 healthy controls. The Dpd and the Dpd/Pyd ratio were elevated (p < 0.0001) in all three conditions compared to controls suggesting that collagen degradation was predominantly from bone. The data suggest that the Ras/MAPK signal transduction pathway is important in bone homeostasis.

Original languageEnglish
Pages (from-to)566-573
Number of pages8
JournalClinical Genetics
Volume80
Issue number6
DOIs
StatePublished - Dec 2011

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Bone Resorption
Mitogen-Activated Protein Kinases
Bone and Bones
Urine
Costello Syndrome
Collagen
Hydroxylysine
Noonan Syndrome
Phenotype
ras Proteins
Neurofibromatosis 1
Metabolic Bone Diseases
Scoliosis
Osteoclasts
deoxypyridinoline
Cartilage
Cell Differentiation
Signal Transduction
Hydrolysis
Homeostasis

Keywords

  • Bone
  • Cardiofaciocutaneous syndrome
  • Costello syndrome
  • Noonan syndrome
  • Pyridinium

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Stevenson, D., Schwarz, E., Carey, J., Viskochil, D., Hanson, H., Bauer, S., ... Pasquali, M. (2011). Bone resorption in syndromes of the Ras/MAPK pathway. Clinical Genetics, 80(6), 566-573. https://doi.org/10.1111/j.1399-0004.2010.01619.x

Bone resorption in syndromes of the Ras/MAPK pathway. / Stevenson, Da; Schwarz, El; Carey, Jc; Viskochil, Dh; Hanson, H.; Bauer, S.; Cindy Weng, H. Y.; Greene, T.; Reinker, K.; Swensen, J.; Chan, Rebecca; Yang, F. C.; Senbanjo, L.; Yang, Z.; Mao, R.; Pasquali, M.

In: Clinical Genetics, Vol. 80, No. 6, 12.2011, p. 566-573.

Research output: Contribution to journalArticle

Stevenson, D, Schwarz, E, Carey, J, Viskochil, D, Hanson, H, Bauer, S, Cindy Weng, HY, Greene, T, Reinker, K, Swensen, J, Chan, R, Yang, FC, Senbanjo, L, Yang, Z, Mao, R & Pasquali, M 2011, 'Bone resorption in syndromes of the Ras/MAPK pathway', Clinical Genetics, vol. 80, no. 6, pp. 566-573. https://doi.org/10.1111/j.1399-0004.2010.01619.x
Stevenson D, Schwarz E, Carey J, Viskochil D, Hanson H, Bauer S et al. Bone resorption in syndromes of the Ras/MAPK pathway. Clinical Genetics. 2011 Dec;80(6):566-573. https://doi.org/10.1111/j.1399-0004.2010.01619.x
Stevenson, Da ; Schwarz, El ; Carey, Jc ; Viskochil, Dh ; Hanson, H. ; Bauer, S. ; Cindy Weng, H. Y. ; Greene, T. ; Reinker, K. ; Swensen, J. ; Chan, Rebecca ; Yang, F. C. ; Senbanjo, L. ; Yang, Z. ; Mao, R. ; Pasquali, M. / Bone resorption in syndromes of the Ras/MAPK pathway. In: Clinical Genetics. 2011 ; Vol. 80, No. 6. pp. 566-573.
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