Mechanisms inducing low bone density in duchenne muscular dystrophy in mice and humans
-
- Anna Rufo
- Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy
-
- Andrea Del Fattore
- Ospedale Pediatrico “Bambino Gesù,” Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
-
- Mattia Capulli
- Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy
-
- Francesco Carvello
- Ospedale Pediatrico “Bambino Gesù,” Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
-
- Loredana De Pasquale
- Ospedale Pediatrico “Bambino Gesù,” Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
-
- Serge Ferrari
- Department of Rehabilitation and Geriatrics, University Hospital, Geneva, Switzerland
-
- Dominique Pierroz
- Department of Rehabilitation and Geriatrics, University Hospital, Geneva, Switzerland
-
- Lucia Morandi
- Muscle Pathology and Immunology Unit, Istituto Neurologico “C. Besta,” Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
-
- Michele De Simone
- Department of Internal Medicine, University Hospital “San Salvatore,” L'Aquila, Italy
-
- Nadia Rucci
- Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy
-
- Enrico Bertini
- Ospedale Pediatrico “Bambino Gesù,” Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
-
- Maria Luisa Bianchi
- Metabolic Unit, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
-
- Fabrizio De Benedetti
- Ospedale Pediatrico “Bambino Gesù,” Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
-
- Anna Teti
- Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy
抄録
<jats:title>Abstract</jats:title> <jats:p>Patients affected by Duchenne muscular dystrophy (DMD) and dystrophic MDX mice were investigated in this study for their bone phenotype and systemic regulators of bone turnover. Micro–computed tomographic (µCT) and histomorphometric analyses showed reduced bone mass and higher osteoclast and bone resorption parameters in MDX mice compared with wild-type mice, whereas osteoblast parameters and mineral apposition rate were lower. In a panel of circulating pro-osteoclastogenic cytokines evaluated in the MDX sera, interleukin 6 (IL-6) was increased compared with wild-type mice. Likewise, DMD patients showed low bone mineral density (BMD) Z-scores and high bone-resorption marker and serum IL-6. Human primary osteoblasts from healthy donors incubated with 10% sera from DMD patients showed decreased nodule mineralization. Many osteogenic genes were downregulated in these cultures, including osterix and osteocalcin, by a mechanism blunted by an IL-6-neutralizing antibody. In contrast, the mRNAs of osteoclastogenic cytokines IL6, IL11, inhibin-βA, and TGFβ2 were increased, although only IL-6 was found to be high in the circulation. Consistently, enhancement of osteoclastogenesis was noted in cultures of circulating mononuclear precursors from DMD patients or from healthy donors cultured in the presence of DMD sera or IL-6. Circulating IL-6 also played a dominant role in osteoclast formation because ex vivo wild-type calvarial bones cultured with 10% sera of MDX mice showed increase osteoclast and bone-resorption parameters that were dampen by treatment with an IL-6 antibody. These results point to IL-6 as an important mediator of bone loss in DMD and suggest that targeted anti-IL-6 therapy may have a positive impact on the bone phenotype in these patients. © 2011 American Society for Bone and Mineral Research</jats:p>
収録刊行物
-
- Journal of Bone and Mineral Research
-
Journal of Bone and Mineral Research 26 (8), 1891-1903, 2011-04-20
Oxford University Press (OUP)
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1361981469971044992
-
- DOI
- 10.1002/jbmr.410
-
- ISSN
- 15234681
- 08840431
-
- データソース種別
-
- Crossref