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Osteogenesis imperfecta: new genes reveal novel mechanisms in bone dysplasia

Published:November 18, 2016DOI:https://doi.org/10.1016/j.trsl.2016.11.005
      Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by fragile bones and short stature and known for its clinical and genetic heterogeneity which is now understood as a collagen-related disorder. During the last decade, research has made remarkable progress in identifying new OI-causing genes and beginning to understand the intertwined molecular and biochemical mechanisms of their gene products. Most cases of OI have dominant inheritance. Each new gene for recessive OI, and a recently identified gene for X-linked OI, has shed new light on its (often previously unsuspected) function in bone biology. Here, we summarize the literature that has contributed to our current understanding of the pathogenesis of OI

      Abbreviations:

      ADAMTS (A disintegrin and metalloprotease with thrombospondin motifs), AR-OI (autosomal recessive osteogenesis imperfecta), ATF6 (activating transcription factor 6), ATGL (adipose triglyceride lipase), BiP (binding immunoglobulin protein), BMDD (bone mineralization density distribution), BMP1 (bone morphogenetic protein-1), BMP2 (bone morphogenetic protein 2), BRIL (bone-restricted interferon-induced transmembrane protein-like), BS (Bruck syndrome), BV/TV (bone volume per tissue volume), bZIP (basic leucine zipper), cKO (conditional knockout), COL1A1 (alpha 1 (I) chains of type I collagen), COL1A2 (alpha 2 (II) chains of type I collagen), CREB3L1 (cyclic AMP responsive element binding protein 3-like 1), CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats- CRISPR associated protein 9), CRTAP (cartilage associated protein), CsA (cyclosporin A), CyPB (cyclophilin B), DKK1 (Dickkopf 1), DXA (dual-energy X-ray absorptiometry), ECM (extracellular matrix), EDS (Ehlers-Danlos syndrome), ER (endoplasmic reticulum), FKBP10 (FK506-binding protein 10), FKBP11 (FK506 binding protein 11), FPRP (prostaglandin F2 receptor inhibitor), FTIR (Fourier transform infrared spectroscopy), GRP94 (glucose regulated protein 94), GVMGFO motif (Gly-Val-Met-Gly-Phe-HyP motif), HIF1α (hypoxia inducible factor 1 alpha), HRD1 (HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase degradation homolog 1), HSP47 (heat shock protein 47), IFITM5 (interferon-induced transmembrane protein 5), IFAP (Ichthyosis Follicularis with Alopecia and Photophobia), IP3R (inositol 1,4,5-trisphosphate receptors), IRE1α (inositol-requiring enzyme 1 alpha), KFSD (keratosis follicularis spinulosa decalvans), KLF10 (Kruppel-like factor 10), LH1 (lysyl hydroxylase 1), LRP5/6 (low-density lipoprotein receptor related protein 5/6), MBTPS1 (membrane-bound transcription factor peptidase, site 1), MBTPS2 (membrane-bound transcription factor peptidase, site 2), MLBRs (multiple ligand binding regions), MSCs (mesenchymal stem cells), mTLD (mammalian talloid), NPDG motif (Asn-Pro-Asp-Gly motif), OASIS (old astrocyte specifically induced substance), OPG (osteoprotegerin), OI (osteogenesis imperfecta), P3H1 (prolyl 3-hydroxylase 1), P4H1 (prolyl 4-hydroxylase), PDI (protein disulfide-isomerase), PEDF (pigment epithelium-derived factor), PEDF-R (pigment epithelium-derived factor receptor), PERK4 (protein kinase RNA-like endoplasmic reticulum kinase 4), PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2), pN-collagen (procollagen type III), PPIase (peptidyl-prolyl cis–trans isomerase), RANKL (receptor activator of nuclear factor kappa-B ligand), rER (rough endoplasmic reticulum), RIP (regulated intramembrane proteolysis), RUNX2 (runt related transcription factor 2), RyR (ryanodine receptor), S1P (site-1 protease), S2P (site-2 protease), SERPINF1 (serine proteinase inhibitor, Clade F, member 1), SPARC (secreted protein, acidic and rich in cysteine), SREBPs (sterol regulatory element binding proteins), TGF-β (transforming growth factor beta), Tgfbr2 (transforming growth factor beta receptor 2), TM (transmembrane), TMEM38B (transmembrane protein 38B), TNF-α (tumor necrosis factor alpha), TRACP-5b (tartrate-resistant acid phosphatase 5b), TRAP (tartrate-resistant acid phosphatase), TRIC (trimeric intracellular cation), TRIC-A (trimeric intracellular cation subtype A), TRIC-B (trimeric intracellular cation subtype B), UPR (unfolded protein response), UTR (untranslated region), WNT1 (wingless-type MMTV (mouse mammary virus tumor) integration site family, member 1), XBP1 (X-box binding protein 1)
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