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Analysis of Nkx3.1:Cre-driven Erk5 deletion reveals a profound spinal deformity which is linked to increased osteoclast activity.
Loveridge, Carolyn J; van 't Hof, Rob J; Charlesworth, Gemma; King, Ayala; Tan, Ee Hong; Rose, Lorraine; Daroszewska, Anna; Prior, Amanda; Ahmad, Imran; Welsh, Michelle; Mui, Ernest J; Ford, Catriona; Salji, Mark; Sansom, Owen; Blyth, Karen; Leung, Hing Y.
Afiliación
  • Loveridge CJ; Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden, Glasgow, G61 1BD, UK.
  • van 't Hof RJ; Beatson Institute for Cancer Research, Bearsden, Glasgow, G61 1BD, UK.
  • Charlesworth G; Institute of Ageing and Chronic Disease, University of Liverpool, WH Duncan Building, West Derby Street, Liverpool, L7 8TX, UK. R.Vanthof@liverpool.ac.uk.
  • King A; Institute of Ageing and Chronic Disease, University of Liverpool, WH Duncan Building, West Derby Street, Liverpool, L7 8TX, UK.
  • Tan EH; Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden, Glasgow, G61 1BD, UK.
  • Rose L; Beatson Institute for Cancer Research, Bearsden, Glasgow, G61 1BD, UK.
  • Daroszewska A; Beatson Institute for Cancer Research, Bearsden, Glasgow, G61 1BD, UK.
  • Prior A; Centre for Molecular Medicine, MRC IGMM, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Ahmad I; Institute of Ageing and Chronic Disease, University of Liverpool, WH Duncan Building, West Derby Street, Liverpool, L7 8TX, UK.
  • Welsh M; Institute of Ageing and Chronic Disease, University of Liverpool, WH Duncan Building, West Derby Street, Liverpool, L7 8TX, UK.
  • Mui EJ; Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden, Glasgow, G61 1BD, UK.
  • Ford C; Beatson Institute for Cancer Research, Bearsden, Glasgow, G61 1BD, UK.
  • Salji M; College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK.
  • Sansom O; Beatson Institute for Cancer Research, Bearsden, Glasgow, G61 1BD, UK.
  • Blyth K; Beatson Institute for Cancer Research, Bearsden, Glasgow, G61 1BD, UK.
  • Leung HY; Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden, Glasgow, G61 1BD, UK.
Sci Rep ; 7(1): 13241, 2017 10 16.
Article en En | MEDLINE | ID: mdl-29038439
Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1:Cre;Erk5 fl/fl (Erk5 fl/fl) mice by ~6-8 weeks of age. X-ray, histological and micro CT (µCT) analyses showed that 100% of male and female Erk5 fl/fl mice had a severely deformed curved thoracic spine, with an associated loss of trabecular bone volume. Although sex-specific differences were observed, histomorphometry measurements revealed that both bone resorption and bone formation parameters were increased in male Erk5 fl/fl mice compared to wild type (WT) littermates. Osteopenia occurs where the rate of bone resorption exceeds that of bone formation, so we investigated the role of the osteoclast compartment. We found that treatment of RANKL-stimulated primary bone marrow-derived macrophage (BMDM) cultures with small molecule ERK5 pathway inhibitors increased osteoclast numbers. Furthermore, osteoclast numbers and expression of osteoclast marker genes were increased in parallel with reduced Erk5 expression in cultures generated from Erk5 fl/fl mice compared to WT mice. Collectively, these results reveal a novel role for Erk5 during bone maturation and homeostasis in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoclastos / Columna Vertebral / Proteína Quinasa 7 Activada por Mitógenos Límite: Animals Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoclastos / Columna Vertebral / Proteína Quinasa 7 Activada por Mitógenos Límite: Animals Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido