Journal ArticleDOI
Mice deficient in Abl are osteoporotic and have defects in osteoblast maturation.
Baojie Li,Sharon Boast,K. De Los Santos,I. Schieren,M. Quiroz,Steven L. Teitelbaum,M. M. Tondravi,M. M. Tondravi,Stephen P. Goff +8 more
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TLDR
It is demonstrated that Abl −/− mice are also osteoporotic, and the long bones of mutant mice contain thinner cortical bone and reduced trabecular bone volume.Abstract:
The c-Abl protein is a non-receptor tyrosine kinase involved in many aspects of mammalian development. c-Abl kinase is widely expressed, but high levels are found in hyaline cartilage in the adult, bone tissue in newborn mice, and osteoblasts and associated neovasculature at sites of endochondrial ossification in the fetus1,2. Mice homozygous for mutations in the gene encoding c-Abl (Abl) display increased perinatal mortality, reduced fertility, foreshortened crania and defects in the maturation of B cells in bone marrow3,4. Here we demonstrate that Abl−/− mice are also osteoporotic. The long bones of mutant mice contain thinner cortical bone and reduced trabecular bone volume. The osteoporotic phenotype is not due to accelerated bone turnover—both the number and activity of osteoclasts are similar to those of control littermates—but rather to dysfunctional osteoblasts. In addition, the rate of mineral apposition in the mutant animals is reduced. Osteoblasts from both stromal and calvarial explants showed delayed maturation in vitro as measured by expression of alkaline phosphatase (ALP), induction of mRNA encoding osteocalcin and mineral deposition.read more
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Crk family adaptors-signalling complex formation and biological roles.
TL;DR: The Crk family adaptors appear to play a role in mediating the action of human oncogenes like the leukaemia-inducing Bcr–Abl protein and this review summarizes some key findings and highlights recent insights.
Journal ArticleDOI
Bone morphogenetic protein-3 is a negative regulator of bone density.
Aaron Daluiski,Thomas Engstrand,Matthew E. Bahamonde,Laura W. Gamer,Eric Agius,SL Stevenson,K. Cox,Rosen,Karen M. Lyons +8 more
TL;DR: BMP3 is an antagonist of osteogenic BMPs: BMP3 dorsalizes Xenopus laevis embryos, inhibits BMP2-mediated induction of Msx2 and blocks BMP1-mediated differentiation of osteoprogenitor cells into osteoblasts, which appear to be mediated through activin receptors.
Journal ArticleDOI
Genetics of Osteoporosis
TL;DR: Find the susceptibility genes underlying osteoporosis requires identifying specific alleles that coinherit with key heritable phenotypes in bone strength, and identification of the genes underlying bone strength in mammals such as the mouse is likely to be of major assistance in human studies.
Journal ArticleDOI
Role of ABL family kinases in cancer: from leukaemia to solid tumours
TL;DR: Enhanced ABL expression and activation in some solid tumours, together with altered cell polarity, invasion or growth induced by activated ABL kinases, suggest that drugs targeting these kinases may be useful for treating selectedSolid tumours.
Journal ArticleDOI
Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage.
TL;DR: The data demonstrate that modification of a transcription coactivator, namely the DNA damage-induced phosphorylation of Yap1 by c-Abl, influences the specificity of target gene activation.
References
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Journal ArticleDOI
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
TL;DR: Cloned cDNA encoding Osf2/Cbfa1 is identified as an osteoblast-specific transcription factor and as a regulator of osteoblasts differentiation.
Journal ArticleDOI
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Makoto Kuro-o,Matsumura Yutaka,Hiroki Aizawa,Hiroshi Kawaguchi,Tatsuo Suga,Toshihiro Utsugi,Yoshio Ohyama,Masahiko Kurabayashi,Tadashi Kaname,Eisuke Kume,Hitoshi Iwasaki,Akihiro Iida,Takako Shiraki-Iida,Satoshi Nishikawa,Ryozo Nagai,Ryozo Nagai,Yo-ichi Nabeshima +16 more
TL;DR: A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes in the mouse, and may function as part of a signalling pathway that regulates ageing in vivo and morbidity in age-related diseases.
Journal ArticleDOI
Cbfa1, a Candidate Gene for Cleidocranial Dysplasia Syndrome, Is Essential for Osteoblast Differentiation and Bone Development
Florian Otto,Anders P Thornell,Tessa Crompton,Angela Denzel,Kimberly C Gilmour,Ian R Rosewell,Gordon Stamp,Rosa S.P Beddington,Stefan Mundlos,Bjorn R. Olsen,Paul B. Selby,Michael John Owen +11 more
TL;DR: The Cbfa1 gene is essential for osteoblast differentiation and bone formation, and the C bfa1 heterozygous mouse is a paradigm for a human skeletal disorder.
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Makoto Kuro-o,Matsumura Yutaka,H. Arawa,Hiroshi Kawaguchi,Tatsuo Suga,Toshihiro Utsugi,Yoshio Ohyama,Masahiko Kurabayashi,Tadashi Kaname,Eisuke Kume,H. Iwasaki,Akihiro Iida,Takako Shiraki-Iida,Satoshi Nishikawa,Ryozo Nagai,Yo-ichi Nabeshima,K. Sharma,L. Kelly,T. Dandekar +18 more
TL;DR: A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes in the mouse, including short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema as mentioned in this paper.
Journal ArticleDOI
Mutations Involving the Transcription Factor CBFA1 Cause Cleidocranial Dysplasia
Stefan Mundlos,Stefan Mundlos,Florian Otto,C Mundlos,C Mundlos,John B. Mulliken,Arthur S. Aylsworth,S Albright,Dick Lindhout,William G. Cole,W Henn,Joan H.M. Knoll,Joan H.M. Knoll,Michael John Owen,Roland Mertelsmann,Bernhard Zabel,Bjorn R. Olsen,Bjorn R. Olsen +17 more
TL;DR: It is concluded that CBFA1 mutations cause Cleidocranial dysplasia and that heterozygous loss of function is sufficient to produce the disorder.