Biglycan in the Skeleton

Small leucine rich proteoglycans (SLRPs), including Biglycan, have key roles in many organ and tissue systems. The goal of this article is to review the function of Biglycan and other related SLRPs in mineralizing tissues of the skeleton. The review is divided into sections that include Biglycan’s role in structural biology, signaling, craniofacial and long bone homeostasis, remodeled skeletal tissues, and in human genetics. While many cell types in the skeleton are now known to be affected by Biglycan, there are still unanswered questions about its mechanism of action(s).

[1]  S. Shibata,et al.  Expression, localization and synthesis of small leucine-rich proteoglycans in developing mouse molar tooth germ , 2020, European journal of histochemistry : EJH.

[2]  L. Schaefer,et al.  Breaking down chronic inflammatory diseases: the role of biglycan in promoting a switch between inflammation and autophagy , 2019, The FEBS journal.

[3]  J. Halper,et al.  Does BMP2 play a role in the pathogenesis of equine degenerative suspensory ligament desmitis? , 2018, BMC Research Notes.

[4]  S. Mundlos,et al.  Impaired proteoglycan glycosylation, elevated TGF-β signaling, and abnormal osteoblast differentiation as the basis for bone fragility in a mouse model for gerodermia osteodysplastica , 2018, PLoS genetics.

[5]  Jean X. Jiang,et al.  Age‐Related Deterioration of Bone Toughness Is Related to Diminishing Amount of Matrix Glycosaminoglycans (GAGs) , 2018, JBMR plus.

[6]  W. Landis,et al.  A Force on the Crown and Tug of War in the Periodontal Complex , 2018, Journal of dental research.

[7]  K. Itoh,et al.  Novel roles of glycosaminoglycans in the degradation of type I collagen by cathepsin K , 2017, Glycobiology.

[8]  N. Bhattacharyya,et al.  Small leucine rich proteoglycans, a novel link to osteoclastogenesis , 2017, Scientific Reports.

[9]  G. Mortier,et al.  Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections , 2016, Genetics in Medicine.

[10]  M. Mörgelin,et al.  The Tyrosine Sulfate Domain of Fibromodulin Binds Collagen and Enhances Fibril Formation* , 2016, The Journal of Biological Chemistry.

[11]  Dongsup Kim,et al.  BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia. , 2016, American journal of human genetics.

[12]  S. Ricard-Blum,et al.  Biglycan potentially regulates angiogenesis during fracture repair by altering expression and function of endostatin. , 2016, Matrix biology : journal of the International Society for Matrix Biology.

[13]  I. Kakizaki,et al.  Chondroitin sulfate cluster of epiphycan from salmon nasal cartilage defines binding specificity to collagens. , 2015, Glycobiology.

[14]  Casie E. Horgan,et al.  Compensatory fetal membrane mechanisms between biglycan and decorin in inflammation , 2015, Molecular reproduction and development.

[15]  M. Somerman,et al.  Fibromodulin and Biglycan Modulate Periodontium through TGFβ/BMP Signaling , 2014, Journal of dental research.

[16]  M. Young,et al.  Biglycan modulates angiogenesis and bone formation during fracture healing. , 2014, Matrix biology : journal of the International Society for Matrix Biology.

[17]  M. Bönecker,et al.  Immunohistochemical expression of biglycan and decorin in the pulp tissue of human primary teeth during resorption. , 2013, Brazilian oral research.

[18]  A. Kariminejad,et al.  Defective initiation of glycosaminoglycan synthesis due to B3GALT6 mutations causes a pleiotropic Ehlers-Danlos-syndrome-like connective tissue disorder. , 2013, American journal of human genetics.

[19]  S. Weinbaum,et al.  Mechanosensation and transduction in osteocytes. , 2013, Bone.

[20]  M. Wendel,et al.  The glycosylation profile of osteoadherin alters during endochondral bone formation. , 2013, Bone.

[21]  Weikai Zhang,et al.  Glycosaminoglycan chains of biglycan promote bone morphogenetic protein-4-induced osteoblast differentiation. , 2012, International journal of molecular medicine.

[22]  K. Hultenby,et al.  Osteoadherin Accumulates in the Predentin towards the Mineralization Front in the Developing Tooth , 2012, PloS one.

[23]  Jennifer J Westendorf,et al.  Update on Wnt signaling in bone cell biology and bone disease. , 2012, Gene.

[24]  J. Gutkind,et al.  Modulation of canonical Wnt signaling by the extracellular matrix component biglycan , 2011, Proceedings of the National Academy of Sciences.

[25]  M. Yamauchi,et al.  Role of glycosaminoglycans of biglycan in BMP-2 signaling. , 2011, Biochemical and biophysical research communications.

[26]  Valerie M. Weaver,et al.  The extracellular matrix at a glance , 2010, Journal of Cell Science.

[27]  Xiaoyan Wang,et al.  Matrix protein biglycan induces osteoblast differentiation through extracellular signal-regulated kinase and Smad pathways. , 2010, Biological & pharmaceutical bulletin.

[28]  R. Iozzo,et al.  Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine‐rich proteoglycans , 2010, The FEBS journal.

[29]  Byoungjae Kim,et al.  Glycan profiling of a defect in decorin glycosylation in equine systemic proteoglycan accumulation, a potential model of progeroid form of Ehlers-Danlos syndrome. , 2010, Archives of biochemistry and biophysics.

[30]  Li Sun,et al.  The Role of FSH and TSH in Bone Loss and Its Clinical Relevance , 2010, Current osteoporosis reports.

[31]  A. Oldberg,et al.  The role of small leucine-rich proteoglycans in collagen fibrillogenesis. , 2010, Matrix biology : journal of the International Society for Matrix Biology.

[32]  Joseph M. Wallace,et al.  Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice , 2010, Annals of Biomedical Engineering.

[33]  M. Karsdal,et al.  Biglycan and fibromodulin have essential roles in regulating chondrogenesis and extracellular matrix turnover in temporomandibular joint osteoarthritis. , 2010, The American journal of pathology.

[34]  D. Heinegård,et al.  The Tyrosine Sulfate-rich Domains of the LRR Proteins Fibromodulin and Osteoadherin Bind Motifs of Basic Clusters in a Variety of Heparin-binding Proteins, Including Bioactive Factors* , 2009, The Journal of Biological Chemistry.

[35]  Pei-hua Wang,et al.  Decorin gene delivery inhibits cardiac fibrosis in spontaneously hypertensive rats by modulation of transforming growth factor-beta/Smad and p38 mitogen-activated protein kinase signaling pathways. , 2009, Human gene therapy.

[36]  J. Pfeilschifter,et al.  Biglycan, a Danger Signal That Activates the NLRP3 Inflammasome via Toll-like and P2X Receptors* , 2009, The Journal of Biological Chemistry.

[37]  Ronald T Raines,et al.  Collagen structure and stability. , 2009, Annual review of biochemistry.

[38]  M. Karsdal,et al.  Local communication on and within bone controls bone remodeling. , 2009, Bone.

[39]  A. Al Haj Zen,et al.  Syndromic and non‐syndromic aneurysms of the human ascending aorta share activation of the Smad2 pathway , 2009, The Journal of pathology.

[40]  A. Kulkarni,et al.  Genetic evidence for key roles of decorin and biglycan in dentin mineralization. , 2009, Matrix biology : journal of the International Society for Matrix Biology.

[41]  R. Iozzo,et al.  Genetic Evidence for the Coordinated Regulation of Collagen Fibrillogenesis in the Cornea by Decorin and Biglycan* , 2009, Journal of Biological Chemistry.

[42]  A. Oldberg,et al.  Homologous Sequence in Lumican and Fibromodulin Leucine-rich Repeat 5-7 Competes for Collagen Binding* , 2009, Journal of Biological Chemistry.

[43]  M. Raspanti,et al.  Glycosaminoglycans show a specific periodic interaction with type I collagen fibrils. , 2008, Journal of structural biology.

[44]  Ego Seeman,et al.  Bone remodelling: its local regulation and the emergence of bone fragility. , 2008, Best practice & research. Clinical endocrinology & metabolism.

[45]  R. Moats,et al.  Biglycan Overexpression on Tooth Enamel Formation in Transgenic Mice , 2008, Anatomical record.

[46]  A. Bhosale,et al.  Articular cartilage: structure, injuries and review of management , 2008 .

[47]  M. Young,et al.  Fibromodulin-Deficient Mice Reveal Dual Functions for Fibromodulin in Regulating Dental Tissue and Alveolar Bone Formation , 2008, Cells Tissues Organs.

[48]  R. Iozzo,et al.  Biological Functions of the Small Leucine-rich Proteoglycans: From Genetics to Signal Transduction* , 2008, Journal of Biological Chemistry.

[49]  D. Vigetti,et al.  Influence of collagen-fibril-based coatings containing decorin and biglycan on osteoblast behavior. , 2008, Journal of biomedical materials research. Part A.

[50]  A. Oldberg,et al.  Fibromodulin Binds Collagen Type I via Glu-353 and Lys-355 in Leucine-rich Repeat 11* , 2007, Journal of Biological Chemistry.

[51]  R. Iozzo,et al.  The glycosaminoglycan chain of decorin plays an important role in collagen fibril formation at the early stages of fibrillogenesis , 2007, The FEBS journal.

[52]  D. Heymann,et al.  Proteoglycans: key partners in bone cell biology , 2007, BioEssays : news and reviews in molecular, cellular and developmental biology.

[53]  M. Young,et al.  Biglycan Deficiency Causes Spontaneous Aortic Dissection and Rupture in Mice , 2007, Circulation.

[54]  R. Iozzo,et al.  Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice. , 2007, Bone.

[55]  Joseph M. Wallace,et al.  Exercise-induced changes in the cortical bone of growing mice are bone- and gender-specific. , 2007, Bone.

[56]  P. Roughley,et al.  SLRP interaction can protect collagen fibrils from cleavage by collagenases. , 2006, Matrix biology : journal of the International Society for Matrix Biology.

[57]  M. Young,et al.  Small leucine-rich proteoglycans in the aging skeleton. , 2006, Journal of musculoskeletal & neuronal interactions.

[58]  D. Scharnweber,et al.  Fibrillogenesis of collagen types I, II, and III with small leucine-rich proteoglycans decorin and biglycan. , 2006, Biomacromolecules.

[59]  Joseph M. Wallace,et al.  The mechanical phenotype of biglycan-deficient mice is bone- and gender-specific. , 2006, Bone.

[60]  M. Young,et al.  Biglycan deficiency increases osteoclast differentiation and activity due to defective osteoblasts. , 2006, Bone.

[61]  A. Oldberg,et al.  Fibromodulin-deficient Mice Display Impaired Collagen Fibrillogenesis in Predentin as Well as Altered Dentin Mineralization and Enamel Formation , 2006, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[62]  A. Zallone,et al.  FSH Directly Regulates Bone Mass , 2006, Cell.

[63]  Ahrar Khan,et al.  Degenerative suspensory ligament desmitis as a systemic disorder characterized by proteoglycan accumulation , 2006, BMC veterinary research.

[64]  L. Kiesel,et al.  Defective glycosylation of decorin and biglycan, altered collagen structure, and abnormal phenotype of the skin fibroblasts of an Ehlers–Danlos syndrome patient carrying the novel Arg270Cys substitution in galactosyltransferase I (β4GalT-7) , 2006, Journal of Molecular Medicine.

[65]  A. Boskey,et al.  Variation in Mineral Properties in Normal and Mutant Bones and Teeth , 2006, Cells Tissues Organs.

[66]  D. Bidwell,et al.  Formation , 2006, Revue Francophone d'Orthoptie.

[67]  M. Young,et al.  Targeted Disruption of Two Small Leucine-rich Proteoglycans, Biglycan and Decorin, Excerpts Divergent Effects on Enamel and Dentin Formation , 2005, Calcified Tissue International.

[68]  A. Holmlund,et al.  Expression of proteoglycan mRNA in patients with painful clicking and chronic closed lock of the temporomandibular joint. , 2005, International journal of oral and maxillofacial surgery.

[69]  C. Stuelten,et al.  Extracellular Matrix Proteoglycans Control the Fate of Bone Marrow Stromal Cells* , 2005, Journal of Biological Chemistry.

[70]  Marian F Young,et al.  The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. , 2005, The Journal of clinical investigation.

[71]  R. Iozzo,et al.  Decorin, a Novel Player in the Insulin-like Growth Factor System* , 2005, Journal of Biological Chemistry.

[72]  H. Larjava,et al.  Colocalization of the collagen-binding proteoglycans decorin, biglycan, fibromodulin and lumican with different cells in human gingiva. , 2005, Journal of periodontal research.

[73]  M. Young,et al.  Transforming growth factor beta stimulation of biglycan gene expression is potentially mediated by sp1 binding factors , 2004, Journal of cellular biochemistry.

[74]  M. Young,et al.  The small leucine‐rich proteoglycan biglycan modulates BMP‐4‐induced osteoblast differentiation , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[75]  H. Sasamura,et al.  Functional characterization of podocan, a member of a new class in the small leucine‐rich repeat protein family , 2004, FEBS letters.

[76]  D. Heinegård,et al.  Identification of Tyrosine Sulfation in Extracellular Leucine-rich Repeat Proteins Using Mass Spectrometry* , 2004, Journal of Biological Chemistry.

[77]  T. L. Andersen,et al.  Biglycan Deficiency Interferes With Ovariectomy‐Induced Bone Loss , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[78]  E. Schönherr,et al.  Differential roles for small leucine-rich proteoglycans in bone formation. , 2003, European cells & materials.

[79]  T. Zorn,et al.  Distribution of biglycan and decorin in rat dental tissue. , 2003, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[80]  J. Balasch Sex steroids and bone: current perspectives. , 2003, Human reproduction update.

[81]  Charlotte Wiberg,et al.  Biglycan Organizes Collagen VI into Hexagonal-like Networks Resembling Tissue Structures* , 2002, The Journal of Biological Chemistry.

[82]  J. Peragallo,et al.  A Syndrome of Joint Laxity and Impaired Tendon Integrity in Lumican- and Fibromodulin-deficient Mice* 210 , 2002, The Journal of Biological Chemistry.

[83]  Marian F Young,et al.  Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases. , 2002, Glycobiology.

[84]  M. Goldberg,et al.  Biglycan is a Repressor of Amelogenin Expression and Enamel Formation: An Emerging Hypothesis , 2002, Journal of dental research.

[85]  A Boyde,et al.  Phenotypic Effects of Biglycan Deficiency Are Linked to Collagen Fibril Abnormalities, Are Synergized by Decorin Deficiency, and Mimic Ehlers‐Danlos‐Like Changes in Bone and Other Connective Tissues , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[86]  M. Young,et al.  Biglycan knockout mice: New models for musculoskeletal diseases , 2002, Glycoconjugate Journal.

[87]  S. Chakravarti Functions of lumican and fibromodulin: Lessons from knockout mice , 2002, Glycoconjugate Journal.

[88]  A. Oldberg,et al.  Abnormal collagen fibrils in tendons of biglycan/fibromodulin‐deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[89]  S. Shi,et al.  Age‐Related Osteoporosis in Biglycan‐Deficient Mice Is Related to Defects in Bone Marrow Stromal Cells , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[90]  D. Arnott,et al.  WISP-1 Binds to Decorin and Biglycan* , 2001, The Journal of Biological Chemistry.

[91]  K. Walsh,et al.  Decorin-mediated Signal Transduction in Endothelial Cells , 2001, The Journal of Biological Chemistry.

[92]  K. Shigemasa,et al.  Gene expression and immunohistochemical localization of decorin and biglycan in association with early bone formation in the developing mandible. , 2001, Journal of oral science.

[93]  K. Uzawa,et al.  Differential expression of decorin and biglycan genes during mouse tooth development. , 2001, Matrix biology : journal of the International Society for Matrix Biology.

[94]  E. Schipani,et al.  Fibromodulin is expressed by both chondrocytes and osteoblasts during fetal bone development , 2001, Journal of cellular biochemistry.

[95]  A. Paterson,et al.  Potential role of modifier genes influencing transforming growth factor-beta1 levels in the development of vascular defects in endoglin heterozygous mice with hereditary hemorrhagic telangiectasia. , 2001, The American journal of pathology.

[96]  E. Vuorio,et al.  Murine fibromodulin: cDNA and genomic structure, and age-related expression and distribution in the knee joint. , 2001, The Biochemical journal.

[97]  Inna Chervoneva,et al.  Differential Expression of Lumican and Fibromodulin Regulate Collagen Fibrillogenesis in Developing Mouse Tendons , 2000, The Journal of cell biology.

[98]  O. Reizes,et al.  Cell Surface Heparan Sulfate Proteoglycans: Selective Regulators of Ligand-Receptor Encounters* , 2000, The Journal of Biological Chemistry.

[99]  J. Braekman,et al.  Triterpene saponins, quaternary ammonium compounds, phosphatidyl cholines, and amino acids in the pronotal and elytral secretions of Platyphora opima and Desmogramma subtropica. , 2000, Journal of natural products.

[100]  H. Väänänen,et al.  The cell biology of osteoclast function. , 2000, Journal of cell science.

[101]  P. Roughley,et al.  Modulation of keratan sulfate synthesis on lumican by the action of cytokines on human articular chondrocytes. , 1999, Matrix biology : journal of the International Society for Matrix Biology.

[102]  F. Reinholt,et al.  Fibromodulin-null Mice Have Abnormal Collagen Fibrils, Tissue Organization, and Altered Lumican Deposition in Tendon* , 1999, The Journal of Biological Chemistry.

[103]  S. Goldstein,et al.  Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice , 1998, Nature Genetics.

[104]  Renato V. Iozzo,et al.  Targeted Disruption of Decorin Leads to Abnormal Collagen Fibril Morphology and Skin Fragility , 1997, Journal of Cell Biology.

[105]  P. Roughley,et al.  Changes with age in the structure of fibromodulin in human articular cartilage. , 1996, Osteoarthritis and cartilage.

[106]  Oldberg,et al.  Decorin-binding Sites for Collagen Type I Are Mainly Located in Leucine-rich Repeats 4-5 (*) , 1995, The Journal of Biological Chemistry.

[107]  M. Young,et al.  The X-chromosomal human biglycan gene BGN is subject to X inactivation but is transcribed like an X-Y homologous gene , 1995, Human Genetics.

[108]  H Kresse,et al.  Interaction of Biglycan with Type I Collagen (*) , 1995, The Journal of Biological Chemistry.

[109]  T Matsumoto,et al.  Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity. , 1994, The Journal of biological chemistry.

[110]  E. Ruoslahti,et al.  Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta. , 1994, The Biochemical journal.

[111]  G Pogány,et al.  The in vitro interaction of proteoglycans with type I collagen is modulated by phosphate. , 1994, Archives of biochemistry and biophysics.

[112]  P. Roughley,et al.  Non-proteoglycan forms of biglycan increase with age in human articular cartilage. , 1993, The Biochemical journal.

[113]  B. Clarke,et al.  Distribution of noncollagenous proteins in the matrix of adult human bone: Evidence of anatomic and functional heterogeneity , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[114]  B. Johnstone,et al.  Identification and characterization of glycanated and non-glycanated forms of biglycan and decorin in the human intervertebral disc. , 1993, The Biochemical journal.

[115]  J. Hassell,et al.  Regulation of corneal collagen fibrillogenesis in vitro by corneal proteoglycan (lumican and decorin) core proteins. , 1993, Experimental eye research.

[116]  T. Hardingham,et al.  Proteoglycans: many forms and many functions , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[117]  M. Young,et al.  Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. , 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[118]  E. Ruoslahti,et al.  Negative regulation of transforming growth factor-β by the proteoglycan decorin , 1990, Nature.

[119]  D. Heinegård,et al.  Specific inhibition of type I and type II collagen fibrillogenesis by the small proteoglycan of tendon. , 1984, The Biochemical journal.

[120]  J. Gallagher,et al.  Specific association of iduronic acid-rich dermatan sulphate with the extracellular matrix of human skin fibroblasts cultured on collagen gels. , 1983, The Biochemical journal.

[121]  J. Keller,et al.  Interactions of cellular glycosaminoglycans with plasma fibronectin and collagen. , 1982, Biochimica et biophysica acta.

[122]  P. Roughley,et al.  O-Linked oligosaccharides of human articular cartilage proteoglycan. , 1982, Biochimica et biophysica acta.

[123]  Frank P Luyten,et al.  Uncovering the periosteum for skeletal regeneration: the stem cell that lies beneath. , 2015, Bone.

[124]  V. Lefebvre,et al.  Vertebrate skeletogenesis. , 2010, Current topics in developmental biology.

[125]  J. Pfeilschifter,et al.  Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin. , 2007, The American journal of pathology.

[126]  M. Yamauchi,et al.  Biglycan is a positive modulator of BMP-2 induced osteoblast differentiation. , 2006, Advances in experimental medicine and biology.

[127]  S. Saika,et al.  Excess biglycan causes eyelid malformation by perturbing muscle development and TGF-α signaling , 2005 .

[128]  S. Saika,et al.  Excess biglycan causes eyelid malformation by perturbing muscle development and TGF-alpha signaling. , 2005, Developmental biology.

[129]  R. Jilka,et al.  Sex steroids and bone. , 2002, Recent progress in hormone research.

[130]  M Goldberg,et al.  Proteoglycans in dentinogenesis. , 2001, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[131]  P. Roughley,et al.  Changes in leucine-rich repeat proteoglycans during maturation of the bovine growth plate. , 2001, Matrix biology : journal of the International Society for Matrix Biology.

[132]  M. Götte,et al.  Functions of cell surface heparan sulfate proteoglycans. , 1999, Annual review of biochemistry.

[133]  P. Robey Vertebrate mineralized matrix proteins: structure and function. , 1996, Connective tissue research.

[134]  E. Ruoslahti,et al.  Negative regulation of transforming growth factor-beta by the proteoglycan decorin. , 1990, Nature.