Searchable abstracts of presentations at key conferences on calcified tissues

ba0001pp500 | Other diseases of bone and mineral metabolism | ECTS2013

IFITM5 c.−14C>T mutation causes variable type V osteogenesis imperfecta phenotype and decreased COL1A1 expression but increased mineralization by cultured proband osteoblasts

Reich Adi , Bae Alison S , Barnes Aileen M , Cabral Wayne A , Chitayat David , Marini Joan C

Introduction: Osteogenesis imperfecta (OI) is a genetically heterogeneous disorder characterized by bone fragility. OI type V, with autosomal dominant inheritance, is characterized by ossification of the forearm interosseus membrane, radiodense metaphyseal bands, propensity for hyperplastic callus formation, and mesh-like lamellation on bone histology. Type V OI probands are reported to have white sclerae and normal teeth. Recent reports identified the cause of type V OI as a ...

ba0005oc6.5 | Development and differentiation (or Aging) | ECTS2016

Absence of cyclophilin A impairs endochondral bone formation by altering intracellular signaling pathways required for osteoblast maturation

Sargent Brandi , Ishikawa Masaki , Clevenger Charles , Yamada Yoshihiko , Cabral Wayne , Marini Joan

Using a CyPB-null mouse model, we previously demonstrated delayed folding, abnormal post-translational modification and altered crosslinking of type I collagen synthesized by osteoblasts. However, intracellular folding of collagen molecules was further delayed by CsA treatment of CyPB-null cells, suggesting involvement of additional PPIases in collagen folding. Since studies of CyPA functions in osteoblasts have not been reported, we investigated the role of this cytoplasmic P...

ba0005p434 | Other diseases of bone and mineral metabolism | ECTS2016

Cyclophilin B deficiency is associated with defective differentiation of bone cell populations and bone hypermineralization

Cabral Wayne , Fratzl-Zelman Nadja , Blouin Stephane , Roschger Paul , Klaushofer Klaus , Marini Joan

Deficiency of Cyclophilin B (CyPB) causes recessively inherited Type IX osteogenesis imperfecta, a moderately severe to lethal bone dysplasia. CyPB, encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that catalyzes the rate-limiting step in collagen folding, and also functions as a component of the collagen prolyl 3-hydroxylation complex. We previously demonstrated in a Ppib−/− mouse model that CyPB PPIase activity r...

ba0001pp501 | Other diseases of bone and mineral metabolism | ECTS2013

Abnormal type I collagen glycosylation pattern and cross-linking in a cyclophilin B KO mouse model of recessive osteogenesis imperfecta

Cabral Wayne , Perdivara Irina , MaryAnn Weis , Terajima Masahiko , Blissett Angela , Chang Weizhong , Makareeva Elena , Leikin Sergey , Eyre David , Yamauchi Mitsuo

Introduction: Recessive osteogenesis imperfecta (OI) is caused by mutations in genes encoding proteins involved in post-translational interactions with type I collagen. Types VII–IX OI involve defects in the collagen prolyl 3-hydroxylation complex, which modifies α1(I)Pro986. PPIB encodes CyPB, a complex component with PPIase activity and the major isomerase facilitating collagen folding. We investigated the role of CyPB in collagen post-translational modifications a...

ba0003cc3 | (1) | ECTS2014

Absence of ER cation channel TMEM38B/TRIC-B causes recessive osteogenesis imperfecta by dysregulation of collagen post-translational modification

Cabral Wayne , Makareeva Elena , Ishikawa Masaki , Barnes Aileen , MaryAnn Weis , Lacbawan Felicitas , Eyre David , Yamada Yoshihiko , Leikin Sergey , Marini Joan

Recessive osteogenesis imperfecta (OI) is caused by mutations in genes encoding proteins involved in post-translational interactions with type I collagen. A founder mutation in a new gene responsible for recessive OI has recently been reported in Bedouins from Israel and Saudi Arabia, who have a homozygous deletion of TMEM38B exon 4 and surrounding intronic sequence. TMEM38B encodes TRIC-B, an integral ER membrane monovalent cation channel involved in Ca...

ba0003pp17 | Bone biomechanics and quality | ECTS2014

Bone fragility and matrix hypermineralization is rescued in homozygous OI Brtl mice mutants

Fratzl-Zelman Nadja , Kozloff Kenneth M , Meganck Jeff , Reich Adi , Roschger Paul , Cabral Wayne , Klaushofer Klaus , Marini Joan

Classical osteogenesis imperfecta (OI) is caused by mutations in the two genes encoding type I collagen. OI is associated with low bone mass and abnormally high bone matrix mineralization. The Brtl/+ OI mouse is a knock-in model caused by a glycine substitution in one COL1A1 allele. Brtl/+ pups display 30% perinatal lethality; survivors have small size and brittle bone. Unexpectedly, homozygous Brtl/Brtl pups, producing only mutant collagen, have normal survival rates...

ba0003pp187 | Genetics | ECTS2014

A novel mutation in IFITM5, encoding BRIL, impairs osteoblast production of PEDF and causes atypical type VI osteogenesis imperfecta

Reich Adi , Farber Charles R , Barnes Aileen M , Becerra Patricia , Rauch Frank , Cabral Wayne A , Bae Alison , Glorieux Francis H , Clemens Thomas L , Marini Joan C

Osteogenesis imperfecta (OI) type V is caused by a unique dominant mutation (c.−14C>T) in IFITM5, which encodes BRIL, a transmembrane ifitm-like protein most strongly expressed in osteoblasts, while type VI OI is caused by recessive null mutations in SERPINF1, encoding pigment epithelium-derived factor (PEDF). We identified a 25-year-old woman with severe OI, whose dermal fibroblasts and cultured osteoblasts displayed minimal secretion of PEDF, but ...

ba0005lb9 | (1) | ECTS2016

First X-linked form of osteogenesis imperfecta, caused by mutations in MBTPS2, demonstrates a fundamental role for regulated intramembrane proteolysis in normal bone formation

Lindert Uschi , Cabral Wayne , Ausavarat Surasawadee , Tongkobpetch Siraprapa , Ludin Katja , Barnes Aileen , Yeetong Patra , Weis Maryann , Krabichler Birgit , Makareeva Elena , Janecke Andreas , Leikin Sergey , Rothlisberger Benno , Rohrback Marianne , Kennerknecht Ingo , Eyre David , Suphapeetiporn Kanya , Giunta Cecilia , Marini Joan , Shotelersuk Vorasuk

Osteogenesis imperfecta (OI) is a heritable bone dysplasia with collagen-related defects. Dominantly inherited OI is caused by structural defects in type I collagen or IFITM5, while recessive forms are caused by deficiency of proteins that interact with collagen for modification, folding or cross-linking. We have identified the first X-linked form of OI, caused by a defect in regulated intramembrane proteolysis (RIP). One type of RIP involves sequential cleavage of regulatory ...