Overexpression of BCLXL in Osteoblasts Inhibits Osteoblast Apoptosis and Increases Bone Volume and Strength.
Journal of Bone and Mineral Research 31(7):1366 (2016)
The Bcl2 family proteins, Bcl2 and BclXL, suppress apoptosis by preventing the release of caspase activators from mitochondria through the inhibition of Bax subfamily proteins. We reported that BCL2 overexpression in osteoblasts using the 2.3 kb Col1a1 promoter increased osteoblast proliferation...
Endoplasmic reticulum stress-mediated apoptosis contributes to a skeletal dysplasia resembling platyspondylic lethal skeletal dysplasia, Torrance type, in a novel Col2a1 mutant mouse line.
Biochemical and Biophysical Research Communicat... 468(1-2):86 (2015)
In humans, mutations in the COL2A1 gene encoding the α1(II) chain of type II collagen, create many clinical phenotypes collectively termed type II collagenopathies. However, the mechanisms generating this diversity remain to be determined. Here we identified a novel Col2a1 mutant mouse line by s...
[Collagen abnormalities and endoplasmic reticulum stress in bone and cartilage].
Clinical calcium 23(11):1635 (2013)
There are many steps in the post-translational modification of collagen molecules. When abnormality occurs in some step, the unfolded collagen molecules are accumulated in the endoplasmic reticulum (ER) , leading to ER stress. ER stress also occurs downstream of the defective modification of col...
Zinc signal: a new player in osteobiology.
Journal of Bone and Mineral Metabolism 31(2):129 (2013)
Disturbed zinc (Zn) homeostasis in mammals is mainly characterized by impaired bone generation accompanied with growth retardation. However, the underlying mechanisms that determine how Zn controls bone homeostasis remain to be defined. Zn homeostasis is tightly controlled by Zn transporter fami...
SP7 inhibits osteoblast differentiation at a late stage in mice.
PLoS ONE 7(3):e32364 (2012)
RUNX2 and SP7 are essential transcription factors for osteoblast differentiation at an early stage. Although RUNX2 inhibits osteoblast differentiation at a late stage, the function of SP7 at the late stage of osteoblast differentiation is not fully elucidated. Thus, we pursued the function of SP...
ENU-induced missense mutation in the C-propeptide coding region of Col2a1 creates a mouse model of platyspondylic lethal skeletal dysplasia, Torrance type.
Mammalian Genome 22(5-6):318 (2011)
The COL2A1 gene encodes the α1(II) chain of the homotrimeric type II collagen, the most abundant protein in cartilage. In humans, COL2A1 mutations create many clinical phenotypes collectively termed type II collagenopathies; however, the genetic basis of the phenotypic diversity is not well eluc...
A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia.
Journal of Human Genetics 56(5):398 (2011)
Desbuquois dysplasia (DBQD) is a severe skeletal dysplasia of autosomal recessive inheritance. DBQD is classified into types 1 and 2 based on presence or absence of hand anomalies. In a previous study, we found a CANT1 (for calcium-activated nucleotidase 1) mutation, c.676G>A in five DBQD famili...
Follistatin-like 1 (Fstl1) is a bone morphogenetic protein (BMP) 4 signaling antagonist in controlling mouse lung development.
PNAS 108(17):7058 (2011)
Lung morphogenesis is a well orchestrated, tightly regulated process through several molecular pathways, including TGF-β/bone morphogenetic protein (BMP) signaling. Alteration of these signaling pathways leads to lung malformation. We investigated the role of Follistatin-like 1 (Fstl1), a secret...
SMOC1 is essential for ocular and limb development in humans and mice.
The American Journal of Human Genetics 88(1):30 (2011)
Microphthalmia with limb anomalies (MLA) is a rare autosomal-recessive disorder, presenting with anophthalmia or microphthalmia and hand and/or foot malformation. We mapped the MLA locus to 14q24 and successfully identified three homozygous (one nonsense and two splice site) mutations in the SPA...
Overexpression of Bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis.
PLoS ONE 6(11):e27487 (2011)
Bcl2 subfamily proteins, including Bcl2 and Bcl-X(L), inhibit apoptosis. As osteoblast apoptosis is in part responsible for osteoporosis in sex steroid deficiency, glucocorticoid excess, and aging, bone loss might be inhibited by the upregulation of Bcl2; however, the effects of Bcl2 overexpress...
CANT1 mutation is also responsible for Desbuquois dysplasia, type 2 and Kim variant.
Journal of Medical Genetics 48(1):32 (2011)
Desbuquois dysplasia (DD) is a recessively inherited condition characterised by short stature, generalised skeletal dysplasia and advanced bone maturation. DD is both clinically and radiographically heterogeneous, and two subtypes have been distinguished based on the presence (type 1) or absence...
Chondroitin sulfate N-acetylgalactosaminyltransferase-1 is required for normal cartilage development.
Biochemical Journal 432(1):47 (2010)
CS (chondroitin sulfate) is a glycosaminoglycan species that is widely distributed in the extracellular matrix. To understand the physiological roles of enzymes involved in CS synthesis, we produced CSGalNAcT1 (CS N-acetylgalactosaminyltransferase 1)-null mice. CS production was reduced by appro...
Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome.
Human Mutation 31(8):966 (2010)
Ehlers-Danlos syndrome (EDS) is a heterogeneous connective tissue disorder involving skin and joint laxity and tissue fragility. A new type of EDS, similar to kyphoscoliosis type but without lysyl hydroxylase deficiency, has been investigated. We have identified a homozygous CHST14 (carbohydrate...
A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility.
Nature Genetics 42(6):515 (2010)
Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here, through a genome-wide association study of rheumatoid arthritis, we identified a polymorphism in CCR6, the gene encoding chemokine (C-C motif) receptor 6 (a surface marker for Th17 cells) at 6q27, that was...
New sequence variants in HLA class II/III region associated with susceptibility to knee osteoarthritis identified by genome-wide association study.
PLoS ONE 5(3):e9723 (2010)
Osteoarthritis (OA) is a common disease that has a definite genetic component. Only a few OA susceptibility genes that have definite functional evidence and replication of association have been reported, however. Through a genome-wide association study and a replication using a total of approxim...
Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation.
Nature Cell Biology 11(10):1205 (2009)
Eukaryotic cells have signalling pathways from the endoplasmic reticulum (ER) to cytosol and nuclei, to avoid excess accumulation of unfolded proteins in the ER. We previously identified a new type of ER stress transducer, OASIS, a bZIP (basic leucine zipper) transcription factor, which is a mem...
Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis.
Nature Cell Biology 11(10):1197 (2009)
Many tissues have a specific signal transduction system for endoplasmic reticulum (ER) dysfunction; however, the mechanisms underlying the ER stress response in cartilage remain unclear. BBF2H7 (BBF2 human homologue on chromosome 7), an ER-resident basic leucine zipper transcription factor, is a...
Association of the tag SNPs in the human SKT gene (KIAA1217) with lumbar disc herniation.
Journal of Bone and Mineral Research 24(9):1537 (2009)
Lumbar disc herniation (LDH) is one of the most common musculo-skeletal diseases. Recent studies have indicated that LDH has strong genetic determinants, and several susceptibility genes have been reported to associate with LDH; however, its etiology and pathogenesis still remain unclear. KIAA12...
Association of KLOTHO gene polymorphisms with knee osteoarthritis in Greek population.
Journal of Orthopaedic Research 26(11):1466 (2008)
Based on the fact that klotho-deficient mice exhibit multiple aging phenotypes, including osteopenia and subchondral sclerosis of joints and on the recent observation that KLOTHO gene plays an important role in calcium/phosphate homeostasis, we explored the possibility whether human KLOTHO gene ...
A functional SNP in EDG2 increases susceptibility to knee osteoarthritis in Japanese.
Human Molecular Genetics 17(12):1790 (2008)
Osteoarthritis (OA) is the most common form of arthritis and is characterized by the gradual loss of articular cartilage. Several OA-susceptibility genes have been identified; however, there are few pharmaceutical targets that can be targeted with small-molecule compounds. To investigate whether...