Biglycan regulates bone development and regeneration

Endochondral bone development and regeneration relies on activation and proliferation of periosteum derived-cells (PDCs). Biglycan (Bgn), a small proteoglycan found in extracellular matrix, is known to be expressed in bone and cartilage, however little is known about its influence during bone develo...

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Main Authors: Reut Shainer, Vardit Kram, Tina M. Kilts, Li Li, Andrew D. Doyle, Inbal Shainer, Daniel Martin, Carl G. Simon, Jinyang Zeng-Brouwers, Liliana Schaefer, Marian F. Young, Genomics and Computational Biology Core
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2023.1119368/full
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author Reut Shainer
Vardit Kram
Tina M. Kilts
Li Li
Andrew D. Doyle
Inbal Shainer
Daniel Martin
Carl G. Simon
Jinyang Zeng-Brouwers
Liliana Schaefer
Marian F. Young
Genomics and Computational Biology Core
author_facet Reut Shainer
Vardit Kram
Tina M. Kilts
Li Li
Andrew D. Doyle
Inbal Shainer
Daniel Martin
Carl G. Simon
Jinyang Zeng-Brouwers
Liliana Schaefer
Marian F. Young
Genomics and Computational Biology Core
author_sort Reut Shainer
collection DOAJ
description Endochondral bone development and regeneration relies on activation and proliferation of periosteum derived-cells (PDCs). Biglycan (Bgn), a small proteoglycan found in extracellular matrix, is known to be expressed in bone and cartilage, however little is known about its influence during bone development. Here we link biglycan with osteoblast maturation starting during embryonic development that later affects bone integrity and strength. Biglycan gene deletion reduced the inflammatory response after fracture, leading to impaired periosteal expansion and callus formation. Using a novel 3D scaffold with PDCs, we found that biglycan could be important for the cartilage phase preceding bone formation. The absence of biglycan led to accelerated bone development with high levels of osteopontin, which appeared to be detrimental to the structural integrity of the bone. Collectively, our study identifies biglycan as an influencing factor in PDCs activation during bone development and bone regeneration after fracture.
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spelling doaj.art-c2bea9f8a1d244e5b70587745ea890de2023-02-16T13:21:36ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-02-011410.3389/fphys.2023.11193681119368Biglycan regulates bone development and regenerationReut Shainer0Vardit Kram1Tina M. Kilts2Li Li3Andrew D. Doyle4Inbal Shainer5Daniel Martin6Carl G. Simon7Jinyang Zeng-Brouwers8Liliana Schaefer9Marian F. Young10Genomics and Computational Biology CoreMolecular Biology of Bones and Teeth Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United StatesMolecular Biology of Bones and Teeth Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United StatesMolecular Biology of Bones and Teeth Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United StatesMolecular Biology of Bones and Teeth Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United StatesNIDCR Imaging Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United StatesDepartment Genes-Circuits-Behavior, Max Planck Institute for Biological Intelligence, Martinsried, GermanyNIDCD/NIDCR Genomics and Computational Biology Core, National Institutes of Health, Bethesda, MD, United StatesBiosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United StatesPharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt, GermanyPharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt, GermanyMolecular Biology of Bones and Teeth Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United StatesEndochondral bone development and regeneration relies on activation and proliferation of periosteum derived-cells (PDCs). Biglycan (Bgn), a small proteoglycan found in extracellular matrix, is known to be expressed in bone and cartilage, however little is known about its influence during bone development. Here we link biglycan with osteoblast maturation starting during embryonic development that later affects bone integrity and strength. Biglycan gene deletion reduced the inflammatory response after fracture, leading to impaired periosteal expansion and callus formation. Using a novel 3D scaffold with PDCs, we found that biglycan could be important for the cartilage phase preceding bone formation. The absence of biglycan led to accelerated bone development with high levels of osteopontin, which appeared to be detrimental to the structural integrity of the bone. Collectively, our study identifies biglycan as an influencing factor in PDCs activation during bone development and bone regeneration after fracture.https://www.frontiersin.org/articles/10.3389/fphys.2023.1119368/fullperiosteumbiglycanextracellular matrixfracturebonecartilage
spellingShingle Reut Shainer
Vardit Kram
Tina M. Kilts
Li Li
Andrew D. Doyle
Inbal Shainer
Daniel Martin
Carl G. Simon
Jinyang Zeng-Brouwers
Liliana Schaefer
Marian F. Young
Genomics and Computational Biology Core
Biglycan regulates bone development and regeneration
Frontiers in Physiology
periosteum
biglycan
extracellular matrix
fracture
bone
cartilage
title Biglycan regulates bone development and regeneration
title_full Biglycan regulates bone development and regeneration
title_fullStr Biglycan regulates bone development and regeneration
title_full_unstemmed Biglycan regulates bone development and regeneration
title_short Biglycan regulates bone development and regeneration
title_sort biglycan regulates bone development and regeneration
topic periosteum
biglycan
extracellular matrix
fracture
bone
cartilage
url https://www.frontiersin.org/articles/10.3389/fphys.2023.1119368/full
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