Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation

Stephen Back, Therese M F Tuohy, Hanqin Chen, Nicholas Wallingford, Andrew Craig, Jaime Struve, Ling Luo Ning, Fatima Banine, Ying Liu, Ansi Chang, Bruce D. Trapp, Bruce F. Bebo, Mahendra S. Rao, Lawrence (Larry) Sherman

Research output: Contribution to journalArticle

373 Citations (Scopus)

Abstract

Demyelination is the hallmark of numerous neurodegenerative conditions, including multiple sclerosis. Oligodendrocyte progenitors (OPCs), which normally mature into myelin-forming oligodendrocytes, are typically present around demyelinated lesions but do not remyelinate affected axons. Here, we find that the glycosaminoglycan hyaluronan accumulates in demyelinated lesions from individuals with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. A high molecular weight (HMW) form of hyaluronan synthesized by astrocytes accumulates in chronic demyelinated lesions. This form of hyaluronan inhibits remyelination after lysolecithin-induced white matter demyelination. OPCs accrue and do not mature into myelin-forming cells in demyelinating lesions where HMW hyaluronan is present. Furthermore, the addition of HMW hyaluronan to OPC cultures reversibly inhibits progenitor-cell maturation, whereas degrading hyaluronan in astrocyte-OPC cocultures promotes oligodendrocyte maturation. HMW hyaluronan may therefore contribute substantially to remyelination failure by preventing the maturation of OPCs that are recruited to demyelinating lesions.

Original languageEnglish (US)
Pages (from-to)966-972
Number of pages7
JournalNature Medicine
Volume11
Issue number9
DOIs
StatePublished - Sep 2005

Fingerprint

Oligodendroglia
Hyaluronic Acid
Molecular Weight
Molecular weight
Demyelinating Diseases
Myelin Sheath
Astrocytes
Multiple Sclerosis
Lysophosphatidylcholines
Autoimmune Experimental Encephalomyelitis
Coculture Techniques
Glycosaminoglycans
Axons
Stem Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. / Back, Stephen; Tuohy, Therese M F; Chen, Hanqin; Wallingford, Nicholas; Craig, Andrew; Struve, Jaime; Ning, Ling Luo; Banine, Fatima; Liu, Ying; Chang, Ansi; Trapp, Bruce D.; Bebo, Bruce F.; Rao, Mahendra S.; Sherman, Lawrence (Larry).

In: Nature Medicine, Vol. 11, No. 9, 09.2005, p. 966-972.

Research output: Contribution to journalArticle

Back, S, Tuohy, TMF, Chen, H, Wallingford, N, Craig, A, Struve, J, Ning, LL, Banine, F, Liu, Y, Chang, A, Trapp, BD, Bebo, BF, Rao, MS & Sherman, LL 2005, 'Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation', Nature Medicine, vol. 11, no. 9, pp. 966-972. https://doi.org/10.1038/nm1279
Back, Stephen ; Tuohy, Therese M F ; Chen, Hanqin ; Wallingford, Nicholas ; Craig, Andrew ; Struve, Jaime ; Ning, Ling Luo ; Banine, Fatima ; Liu, Ying ; Chang, Ansi ; Trapp, Bruce D. ; Bebo, Bruce F. ; Rao, Mahendra S. ; Sherman, Lawrence (Larry). / Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. In: Nature Medicine. 2005 ; Vol. 11, No. 9. pp. 966-972.
@article{321c7b10e3d748d995a0c9c7aeec127c,
title = "Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation",
abstract = "Demyelination is the hallmark of numerous neurodegenerative conditions, including multiple sclerosis. Oligodendrocyte progenitors (OPCs), which normally mature into myelin-forming oligodendrocytes, are typically present around demyelinated lesions but do not remyelinate affected axons. Here, we find that the glycosaminoglycan hyaluronan accumulates in demyelinated lesions from individuals with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. A high molecular weight (HMW) form of hyaluronan synthesized by astrocytes accumulates in chronic demyelinated lesions. This form of hyaluronan inhibits remyelination after lysolecithin-induced white matter demyelination. OPCs accrue and do not mature into myelin-forming cells in demyelinating lesions where HMW hyaluronan is present. Furthermore, the addition of HMW hyaluronan to OPC cultures reversibly inhibits progenitor-cell maturation, whereas degrading hyaluronan in astrocyte-OPC cocultures promotes oligodendrocyte maturation. HMW hyaluronan may therefore contribute substantially to remyelination failure by preventing the maturation of OPCs that are recruited to demyelinating lesions.",
author = "Stephen Back and Tuohy, {Therese M F} and Hanqin Chen and Nicholas Wallingford and Andrew Craig and Jaime Struve and Ning, {Ling Luo} and Fatima Banine and Ying Liu and Ansi Chang and Trapp, {Bruce D.} and Bebo, {Bruce F.} and Rao, {Mahendra S.} and Sherman, {Lawrence (Larry)}",
year = "2005",
month = "9",
doi = "10.1038/nm1279",
language = "English (US)",
volume = "11",
pages = "966--972",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation

AU - Back, Stephen

AU - Tuohy, Therese M F

AU - Chen, Hanqin

AU - Wallingford, Nicholas

AU - Craig, Andrew

AU - Struve, Jaime

AU - Ning, Ling Luo

AU - Banine, Fatima

AU - Liu, Ying

AU - Chang, Ansi

AU - Trapp, Bruce D.

AU - Bebo, Bruce F.

AU - Rao, Mahendra S.

AU - Sherman, Lawrence (Larry)

PY - 2005/9

Y1 - 2005/9

N2 - Demyelination is the hallmark of numerous neurodegenerative conditions, including multiple sclerosis. Oligodendrocyte progenitors (OPCs), which normally mature into myelin-forming oligodendrocytes, are typically present around demyelinated lesions but do not remyelinate affected axons. Here, we find that the glycosaminoglycan hyaluronan accumulates in demyelinated lesions from individuals with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. A high molecular weight (HMW) form of hyaluronan synthesized by astrocytes accumulates in chronic demyelinated lesions. This form of hyaluronan inhibits remyelination after lysolecithin-induced white matter demyelination. OPCs accrue and do not mature into myelin-forming cells in demyelinating lesions where HMW hyaluronan is present. Furthermore, the addition of HMW hyaluronan to OPC cultures reversibly inhibits progenitor-cell maturation, whereas degrading hyaluronan in astrocyte-OPC cocultures promotes oligodendrocyte maturation. HMW hyaluronan may therefore contribute substantially to remyelination failure by preventing the maturation of OPCs that are recruited to demyelinating lesions.

AB - Demyelination is the hallmark of numerous neurodegenerative conditions, including multiple sclerosis. Oligodendrocyte progenitors (OPCs), which normally mature into myelin-forming oligodendrocytes, are typically present around demyelinated lesions but do not remyelinate affected axons. Here, we find that the glycosaminoglycan hyaluronan accumulates in demyelinated lesions from individuals with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. A high molecular weight (HMW) form of hyaluronan synthesized by astrocytes accumulates in chronic demyelinated lesions. This form of hyaluronan inhibits remyelination after lysolecithin-induced white matter demyelination. OPCs accrue and do not mature into myelin-forming cells in demyelinating lesions where HMW hyaluronan is present. Furthermore, the addition of HMW hyaluronan to OPC cultures reversibly inhibits progenitor-cell maturation, whereas degrading hyaluronan in astrocyte-OPC cocultures promotes oligodendrocyte maturation. HMW hyaluronan may therefore contribute substantially to remyelination failure by preventing the maturation of OPCs that are recruited to demyelinating lesions.

UR - http://www.scopus.com/inward/record.url?scp=24744468983&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24744468983&partnerID=8YFLogxK

U2 - 10.1038/nm1279

DO - 10.1038/nm1279

M3 - Article

C2 - 16086023

AN - SCOPUS:24744468983

VL - 11

SP - 966

EP - 972

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 9

ER -