Astrocytes from the Contused Spinal Cord Inhibit Oligodendrocyte Differentiation of Adult Oligodendrocyte Precursor Cells by Increasing the Expression of Bone Morphogenetic Proteins

Overview

Journal J Neurosci

Specialty Neurology

Date 2011 Apr 22

PMID 21508230

Citations 94

Authors

Yaping Wang

Xiaoxin Cheng

Qian He

Yiyan Zheng

Dong H Kim

Scott R Whittemore

Qilin L Cao

Affiliations

Soon will be listed here.

Abstract

Promotion of remyelination is an important therapeutic strategy to facilitate functional recovery after traumatic spinal cord injury (SCI). Transplantation of neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) has been used to enhance remyelination after SCI. However, the microenvironment in the injured spinal cord is inhibitory for oligodendrocyte (OL) differentiation of NSCs or OPCs. Identifying the signaling pathways that inhibit OL differentiation in the injured spinal cord could lead to new therapeutic strategies to enhance remyelination and functional recovery after SCI. In the present study, we show that reactive astrocytes from the injured rat spinal cord or their conditioned media inhibit OL differentiation of adult OPCs with concurrent promotion of astrocyte differentiation. The expression of bone morphogenetic proteins (BMP) is dramatically increased in the reactive astrocytes and their conditioned media. Importantly, blocking BMP activity by BMP receptor antagonist, noggin, reverse the effects of active astrocytes on OPC differentiation by increasing the differentiation of OL from OPCs while decreasing the generation of astrocytes. These data indicate that the upregulated bone morphogenetic proteins in the reactive astrocytes are major factors to inhibit OL differentiation of OPCs and to promote its astrocyte differentiation. These data suggest that manipulation of BMP signaling in the endogenous or grafted NSCs or OPCs may be a useful therapeutic strategy to increase their OL differentiation and remyelination and enhance functional recovery after SCI.

Citing Articles

NLRX1 limits inflammatory neurodegeneration in the anterior visual pathway.

Gill A, Smith M, Galleguillos D, Garton T, Mace J, Gadani S J Neuroinflammation. 2025; 22(1):21.

PMID: 39875919 PMC: 11773851. DOI: 10.1186/s12974-025-03339-0.

Generalized Epileptic Seizures in Fibrodysplasia Ossificans Progressiva Harboring a Recurrent Heterozygous Variant of the Gene (R206H).

Mishima K, Kitoh H, Shiraki A, Sawamura K, Kamiya Y, Matsushita M Case Rep Genet. 2024; 2024:9569275.

PMID: 39719967 PMC: 11668544. DOI: 10.1155/crig/9569275.

Early Postnatal Neuroinflammation Produces Key Features of Diffuse Brain White Matter Injury in Rats.

Waddell J, Lin S, Carter K, Truong T, Hebert M, Ojeda N Brain Sci. 2024; 14(10).

PMID: 39451991 PMC: 11505921. DOI: 10.3390/brainsci14100976.

Astrocyte-Neuron Interactions in Spinal Cord Injury.

Reyes C, Mokalled M Adv Neurobiol. 2024; 39:213-231.

PMID: 39190077 PMC: 11684398. DOI: 10.1007/978-3-031-64839-7_9.

From Physiology to Pathology of Astrocytes: Highlighting Their Potential as Therapeutic Targets for CNS Injury.

Yuan Y, Liu H, Dai Z, He C, Qin S, Su Z Neurosci Bull. 2024; 41(1):131-154.

PMID: 39080102 PMC: 11748647. DOI: 10.1007/s12264-024-01258-3.

References

Hall A, Miller R . Emerging roles for bone morphogenetic proteins in central nervous system glial biology. J Neurosci Res. 2004; 76(1):1-8. DOI: 10.1002/jnr.20019. View

Keirstead H, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K . Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci. 2005; 25(19):4694-705. PMC: 6724772. DOI: 10.1523/JNEUROSCI.0311-05.2005. View

Williams A, Piaton G, Lubetzki C . Astrocytes--friends or foes in multiple sclerosis?. Glia. 2007; 55(13):1300-12. DOI: 10.1002/glia.20546. View

Cheng X, Wang Y, He Q, Qiu M, Whittemore S, Cao Q . Bone morphogenetic protein signaling and olig1/2 interact to regulate the differentiation and maturation of adult oligodendrocyte precursor cells. Stem Cells. 2007; 25(12):3204-14. PMC: 2742907. DOI: 10.1634/stemcells.2007-0284. View

Wang S, Sdrulla A, Disibio G, Bush G, Nofziger D, Hicks C . Notch receptor activation inhibits oligodendrocyte differentiation. Neuron. 1998; 21(1):63-75. DOI: 10.1016/s0896-6273(00)80515-2. View

Trapp B, Nave K . Multiple sclerosis: an immune or neurodegenerative disorder?. Annu Rev Neurosci. 2008; 31:247-69. DOI: 10.1146/annurev.neuro.30.051606.094313. View

Foote A, Blakemore W . Inflammation stimulates remyelination in areas of chronic demyelination. Brain. 2005; 128(Pt 3):528-39. DOI: 10.1093/brain/awh417. View

See J, Zhang X, Eraydin N, Mun S, Mamontov P, Golden J . Oligodendrocyte maturation is inhibited by bone morphogenetic protein. Mol Cell Neurosci. 2004; 26(4):481-92. DOI: 10.1016/j.mcn.2004.04.004. View

Wada T, Kagawa T, Ivanova A, Zalc B, Shirasaki R, Murakami F . Dorsal spinal cord inhibits oligodendrocyte development. Dev Biol. 2000; 227(1):42-55. DOI: 10.1006/dbio.2000.9869. View

10.

Fukuda S, Kondo T, Takebayashi H, Taga T . Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the astrocytic differentiation pathway. Cell Death Differ. 2003; 11(2):196-202. DOI: 10.1038/sj.cdd.4401332. View

11.

Fuller M, DeChant A, Rothstein B, Caprariello A, Wang R, Hall A . Bone morphogenetic proteins promote gliosis in demyelinating spinal cord lesions. Ann Neurol. 2007; 62(3):288-300. DOI: 10.1002/ana.21179. View

12.

Blakemore W, Gilson J, Crang A . The presence of astrocytes in areas of demyelination influences remyelination following transplantation of oligodendrocyte progenitors. Exp Neurol. 2004; 184(2):955-63. DOI: 10.1016/S0014-4886(03)00347-9. View

13.

Anderson J, Hampton D, Patani R, Pryce G, Crowther R, Reynolds R . Abnormally phosphorylated tau is associated with neuronal and axonal loss in experimental autoimmune encephalomyelitis and multiple sclerosis. Brain. 2008; 131(Pt 7):1736-48. DOI: 10.1093/brain/awn119. View

14.

Liedtke W, Edelmann W, Bieri P, Chiu F, Cowan N, Kucherlapati R . GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron. 1996; 17(4):607-15. DOI: 10.1016/s0896-6273(00)80194-4. View

15.

Ara J, See J, Mamontov P, Hahn A, Bannerman P, Pleasure D . Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitis. J Neurosci Res. 2007; 86(1):125-35. DOI: 10.1002/jnr.21462. View

16.

Franklin R, ffrench-Constant C . Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci. 2008; 9(11):839-55. DOI: 10.1038/nrn2480. View

17.

John G, Shankar S, Shafit-Zagardo B, Massimi A, Lee S, Raine C . Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med. 2002; 8(10):1115-21. DOI: 10.1038/nm781. View

18.

Wolswijk G . Oligodendrocyte precursor cells in the demyelinated multiple sclerosis spinal cord. Brain. 2002; 125(Pt 2):338-49. DOI: 10.1093/brain/awf031. View

19.

Chang A, Tourtellotte W, Rudick R, Trapp B . Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med. 2002; 346(3):165-73. DOI: 10.1056/NEJMoa010994. View

20.

Wilson H, Scolding N, Raine C . Co-expression of PDGF alpha receptor and NG2 by oligodendrocyte precursors in human CNS and multiple sclerosis lesions. J Neuroimmunol. 2006; 176(1-2):162-73. DOI: 10.1016/j.jneuroim.2006.04.014. View