Comment on: PH20 is not expressed in murine CNS and oligodendrocyte precursor cells

Sherman, Larry S.; Back, Stephen A.

doi:10.1002/acn3.430

Cited by 2 publications

(4 citation statements)

References 6 publications

(11 reference statements)

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“…Thus, signaling by HA through CD44 or other HA receptors (e.g., toll-like receptors; Black et al, 2013;Campo et al, 2012;Foley et al, 2012;Garantziotis et al, 2010;Jiang et al, 2005;Li, Potts-Kant, Garantziotis, Foster, & Hollingsworth, 2011;Liang et al, 2016;Riehl, Santhanam, Foster, Ciorba, & Stenson, 2015;Scheibner et al, 2006;Sloane et al, 2010;Srivastava et al, 2018;Sunabori, Koike, Asari, Oonuki, & Uchiyama, 2016;Taylor et al, 2007;Termeer et al, 2002) The specific hyaluronidase or hyaluronidases which generate HA digestion products that block OPC maturation are unknown. We and others reported that the PH20 hyaluronidase is transiently expressed following a variety of insults to the CNS (Hagen et al, 2014;Preston et al, 2013;Sherman & Back, 2017;Sloane et al, 2010;Xing et al, 2014). However, in our experience PH20 transcripts are only expressed transiently and at very low abundance in injured CNS tissues (unpublished findings).…”

Section: Discussionsupporting

confidence: 51%

“…The specific hyaluronidase or hyaluronidases which generate HA digestion products that block OPC maturation are unknown. We and others reported that the PH20 hyaluronidase is transiently expressed following a variety of insults to the CNS (Hagen et al, ; Preston et al, ; Sherman & Back, ; Sloane et al, ; Xing et al, ). However, in our experience PH20 transcripts are only expressed transiently and at very low abundance in injured CNS tissues (unpublished findings).…”

Section: Discussionmentioning

confidence: 88%

“…We also found that digestion products of HA in a specific size range blocked remyelination in vitro and in vivo (Preston et al, ; Srivastava et al, ). Hyal5 has not been detected in OPCs or in the CNS (Preston et al, ) while PH20 RNA has been reported to only be transiently expressed by OPCs or other cells, especially following CNS insults (Hagen et al, ; Preston et al, ; Sherman & Back, ; Sloane et al, ; Xing et al, ). However, other reports have failed to find PH20 expression in OPCs or in demyelinating lesions and one study indicated that a pegylated form of recombinant human PH20 failed to influence OPC maturation (Marella et al, ; but see Sherman & Back, ).…”

Section: Introductionmentioning

confidence: 99%

“…Hyal5 has not been detected in OPCs or in the CNS (Preston et al, 2013) while PH20 RNA has been reported to only be transiently expressed by OPCs or other cells, especially following CNS insults (Hagen et al, 2014;Preston et al, 2013;Sherman & Back, 2017;Sloane et al, 2010;Xing et al, 2014). However, other reports have failed to find PH20 expression in OPCs or in demyelinating lesions and one study indicated that a pegylated form of recombinant human PH20 failed to influence OPC maturation (Marella et al, 2017; but see Sherman & Back, 2017). In contrast, TMEM-2 has been detected in OL lineage cells (Golan et al, 2008;Marques et al, 2016) and CEMIP is widely expressed in the brain and is elevated in demyelinating lesions (Marella et al, 2018;Yoshino et al, 2017).…”

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confidence: 99%

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A modified flavonoid accelerates oligodendrocyte maturation and functional remyelination

Matsumoto

Banine

et al. 2019

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Myelination delay and remyelination failure following insults to the central nervous system (CNS) impede axonal conduction and lead to motor, sensory and cognitive impairments. Both myelination and remyelination are often inhibited or delayed due to the failure of oligodendrocyte progenitor cells (OPCs) to mature into myelinating oligodendrocytes (OLs). Digestion products of the glycosaminoglycan hyaluronan (HA) have been implicated in blocking OPC maturation, but how these digestion products are generated is unclear. We tested the possibility that hyaluronidase activity is directly linked to the inhibition of OPC maturation by developing a novel modified flavonoid that functions as a hyaluronidase inhibitor. This compound, called S3, blocks some but not all hyaluronidases and only inhibits matrix metalloproteinase activity at high concentrations. We find that S3 reverses HA‐mediated inhibition of OPC maturation in vitro, an effect that can be overcome by excess recombinant hyaluronidase. Furthermore, we find that hyaluronidase inhibition by S3 accelerates OPC maturation in an in vitro model of perinatal white matter injury. Finally, blocking hyaluronidase activity with S3 promotes functional remyelination in mice with lysolecithin‐induced demyelinating corpus callosum lesions. All together, these findings support the notion that hyaluronidase activity originating from OPCs in CNS lesions is sufficient to prevent OPC maturation, which delays myelination or blocks remyelination. These data also indicate that modified flavonoids can act as selective inhibitors of hyaluronidase activity and can promote OPC maturation, making them excellent candidates to accelerate myelination or promote remyelination following perinatal and adult CNS insults.

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