Brittle bone disease research suggests new approach to therapy
The outcome of the study was announced today by Elena Makareeva, of the NICHD, at ECTS 2017, the 44th European Calcified Tissue Society Congress being held in Salzburg, Austria.
autophagy of misfolded procollagen plays an important role in brittle bone disease. It might be ... targeted for therapeutic intervention
"The G610C mouse with a Gly610 to Cys substitution in the α2(I) chain produces moderately severe osteogenesis imperfecta (OI) in heterozygous animals and lethal OI in homozygous animals. To modulate autophagy, we crossed G610C with Atg5flox/flox (MGI:3663625) mice and then generated G610C;Atg5flox/flox;osteocalcin-Cre animals by breeding with osteocalcin-Cre mice (MGI:2446069).
"Even without introducing Cre recombinase, we found Atg5 mRNA and protein expression to be 2-5 times lower in all tested tissues of Atg5flox/flox compared to Atg5+/+ animals (p less than 0.05). Lower expression of the Atg5 protein, which is required for autophagosome membrane formation, significantly increased the frequency and severity of skeletal deformities in newborn G610C-het pups and reduced survival of the pups by 30-50% without affecting their wild type littermates.
Dr Makareeva concluded: "Combined with our other observations, this study suggests that autophagy of misfolded procollagen plays an important role in brittle bone disease. It might be responsible for variable severity of the same mutation in different individuals and be targeted for therapeutic intervention."
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Notes for editors
About the study
The objective was to assess how autophagy modulation by genetic tools affects bone phenotype and the conclusion was that the study, combined with the researchers' other observations, suggests that autophagy of misfolded procollagen plays an important role in OI bone pathology. It might be responsible for variable severity of the same mutation in different individuals and be targeted for therapeutic intervention.
About ECTS 2017 (http://ects2017.org)
ECTS serves as a forum for researchers and clinicians working in the musculoskeletal field to join forces, discover and discuss the latest advances and controversies in research and in the daily care of patients.
About The European Calcified Tissue Society (http://www.ectsoc.org/)
Calcified tissues are central to a healthy skeleton and to bone disorders - such as osteoporosis, back pain and fractures - that make life a misery for countless people. Children can inherit some forms of bone diseases causing bone pain, shortness and deformed limbs.
For further information please contact
Roberta Mugnai, ECTS executive director
Tel: + 32 476 520 716
ECTS 2017: http://ects2017.org
Event hashtag: #ECTS2017 http://bit.ly/ECTS17-BB
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