Role of Chondroitin Sulfation Following Spinal Cord Injury

Hussein, Rowan K; Mencio, Caitlin; Katagiri, Yasuhiro; Brake, Alexis M; Geller, Herbert M.

doi:10.3389/fncel.2020.00208

Cited by 37 publications

(33 citation statements)

References 146 publications

(193 reference statements)

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“…In this context, the contemporary in vitro supplementation of both GAGs may represent a more physiological environment for chondrocyte differentiation. Some scientists suggest that GAGs have a "sulfation code" whereby they encode functional information (Gama et al, 2006;Nandini and Sugahara, 2006;Hussein et al, 2020). For this reason, we used bCS and fCS that have different lengths and sulfation patterns and compared them with BC that is unsulfated.…”

Section: Discussionmentioning

confidence: 99%

Timely Supplementation of Hydrogels Containing Sulfated or Unsulfated Chondroitin and Hyaluronic Acid Affects Mesenchymal Stromal Cells Commitment Toward Chondrogenic Differentiation

Alessio

Stellavato

Aprile

et al. 2021

Front. Cell Dev. Biol.

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Mesenchymal stromal cells (MSCs) are currently used for cartilage cell therapy because of their well proven capacity to differentiate in chondrocytes. The advantage of MSC-based therapy is the possibility of producing a high number of chondrocytes for implants. The transplant procedure, however, has some limitations, since MSCs may produce non-functional chondrocytes. This limit has been challenged by cultivating MSC in media with hydrogels containing hyaluronic acid (HA), extractive chondroitin sulfate (CS), or bio-fermentative unsulphated chondroitin (BC) alone or in combination. Nevertheless, a clear study of the effect of glycosaminoglycans (GAGs) on chondrocyte differentiation is still lacking, especially for the newly obtained unsulfated chondroitin of biotechnological origin. Are these GAGs playing a role in the commitment of stem cells to chondrocyte progenitors and in the differentiation of progenitors to mature chondrocytes? Alternatively, do they have a role only in one of these biological processes? We evaluated the role of HA, CS, and – above all – BC in cell commitment and chondrocyte differentiation of MSCs by supplementing these GAGs in different phases of in vitro cultivation. Our data provided evidence that a combination of HA and CS or of HA and BC supplemented during the terminal in vitro differentiation and not during cell commitment of MSCs improved chondrocytes differentiation without the presence of fibrosis (reduced expression of Type I collagen). This result suggests that a careful evaluation of extracellular cues for chondrocyte differentiation is fundamental to obtaining a proper maturation process.

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Section: Discussionmentioning

confidence: 99%

Timely Supplementation of Hydrogels Containing Sulfated or Unsulfated Chondroitin and Hyaluronic Acid Affects Mesenchymal Stromal Cells Commitment Toward Chondrogenic Differentiation

Alessio

Stellavato

Aprile

et al. 2021

Front. Cell Dev. Biol.

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“…Apart from their involvement in cancer, CSPGs are also in focus of other research areas, including neurogenesis and spinal cord injury ( Maeda, 2015 ). Following damage to the central nervous system, axons fail to regenerate due to the formation of a glial scar, which is composed of extracellular matrix components including CSPGs ( Hussein et al, 2020 ). The production of several CSPG family members is differentially regulated in the glial scar as neurocan, brevican and versican are increased, while aggrecan is reduced ( Mukhamedshina et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…CSPGs are important components in connective tissue and fine-tunes a wide range of cellular processes, including neural development, growth factor signaling and inflammation ( Hatano and Watanabe, 2020 ; Hussein et al, 2020 ). However, the structural identification of CSPGs is often difficult, as the identification requires the combined sequencing of specific core proteins together with the structural verification of any potential CS polysaccharides.…”

Section: Introductionmentioning

confidence: 99%

Expanding the Chondroitin Sulfate Glycoproteome — But How Far?

Noborn

Nikpour

Persson

et al. 2021

Front. Cell Dev. Biol.

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Chondroitin sulfate proteoglycans (CSPGs) are found at cell surfaces and in connective tissues, where they interact with a multitude of proteins involved in various pathophysiological processes. From a methodological perspective, the identification of CSPGs is challenging, as the identification requires the combined sequencing of specific core proteins, together with the characterization of the CS polysaccharide modification(s). According to the current notion of CSPGs, they are often considered in relation to a functional role in which a given proteoglycan regulates a specific function in cellular physiology. Recent advances in glycoproteomic methods have, however, enabled the identification of numerous novel chondroitin sulfate core proteins, and their glycosaminoglycan attachment sites, in humans and in various animal models. In addition, these methods have revealed unexpected structural complexity even in the linkage regions. These findings indicate that the number and structural complexity of CSPGs are much greater than previously perceived. In light of these findings, the prospect of finding additional CSPGs, using improved methods for structural and functional characterizations, and studying novel sample matrices in humans and in animal models is discussed. Further, as many of the novel CSPGs are found in low abundance and with not yet assigned functions, these findings may challenge the traditional notion of defining proteoglycans. Therefore, the concept of proteoglycans is considered, discussing whether “a proteoglycan” should be defined mainly on the basis of an assigned function or on the structural evidence of its existence.

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“…These effects on axonal growth depend on the length of the sulfated disaccharide sequence of the proteoglycans and their position in the glycan chain ( 40 ). In the chronic phase after central nervous system injury, accumulated CS proteoglycans in glial scar hinder axonal regeneration ( 43 , 44 ). However, the role of CS (and HS) degradation in the acute phase (in this study) of glial scar formation remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Ischemic stroke disrupts the endothelial glycocalyx through activation of proHPSE via acrolein exposure

Suzuki

Ishikawa

et al. 2020

Journal of Biological Chemistry

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Infiltration of peripheral immune cells after blood-brain barrier dysfunction causes severe inflammation after a stroke. Although the endothelial glycocalyx — a network of membrane-bound glycoproteins and proteoglycans that covers the lumen of endothelial cells — functions as a barrier to circulating cells, the relationship between stroke severity and glycocalyx dysfunction remains unclear. In this study, glycosaminoglycans (GAGs), a component of the endothelial glycocalyx, were studied in the context of ischemic stroke using a photochemically induced thrombosis (PIT) mouse model. Decreased levels of heparan sulfate and chondroitin sulfate and increased activity of hyaluronidase 1 and heparanase (HPSE) were observed in ischemic brain tissues. HPSE expression in cerebral vessels increased after stroke onset and infarct volume greatly decreased after co-administration of N-acetylcysteine (NAC)+GAG oligosaccharides as compared to NAC administration alone. These results suggest that the endothelial glycocalyx was injured after the onset of stroke. Interestingly, scission activity of proHPSE produced by immortalized endothelial cells and HEK293 cells transfected with hHPSE1 cDNA were activated by acrolein (ACR) exposure. We identified the ACR modified amino acid residues of proHPSE using nano LC-MS/MS, suggesting that ACR modification of Lys139 (6- kDa linker), and Lys107 and Lys161, located in the immediate vicinity of the 6-kDa linker, at least in part, is attributed to the activation of proHPSE. Since proHPSE, but not HPSE, localizes outside cells by binding with HS proteoglycans, ACR-modified proHPSE represents a promising target to protect the endothelial glycocalyx.

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Role of Chondroitin Sulfation Following Spinal Cord Injury

Cited by 37 publications

References 146 publications

Timely Supplementation of Hydrogels Containing Sulfated or Unsulfated Chondroitin and Hyaluronic Acid Affects Mesenchymal Stromal Cells Commitment Toward Chondrogenic Differentiation

Timely Supplementation of Hydrogels Containing Sulfated or Unsulfated Chondroitin and Hyaluronic Acid Affects Mesenchymal Stromal Cells Commitment Toward Chondrogenic Differentiation

Expanding the Chondroitin Sulfate Glycoproteome — But How Far?

Ischemic stroke disrupts the endothelial glycocalyx through activation of proHPSE via acrolein exposure

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