Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican
We have examined the effect of exogenous linear chain high molecular weight hyaluronic acid (HMW HA) on endogenously synthesized hyaluronic acid (HA) and associated binding proteins in primary cultures of fibroblast-like stromal cells that were obtained by collagenase digestion of the murine peripat...
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MDPI AG
2020-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/7/1681 |
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| author | Jiapeng Xue Jinnan Chen Quan Shen Deva Chan Jun Li Adam P. Tanguay Tannin A. Schmidt Faizan Niazi Anna Plaas |
| author_facet | Jiapeng Xue Jinnan Chen Quan Shen Deva Chan Jun Li Adam P. Tanguay Tannin A. Schmidt Faizan Niazi Anna Plaas |
| author_sort | Jiapeng Xue |
| collection | DOAJ |
| description | We have examined the effect of exogenous linear chain high molecular weight hyaluronic acid (HMW HA) on endogenously synthesized hyaluronic acid (HA) and associated binding proteins in primary cultures of fibroblast-like stromal cells that were obtained by collagenase digestion of the murine peripatellar fat pad. The cultures were expanded in DMEM that was supplemented with fetal bovine serum and basic fibroblast growth factor (bFGF) then exposed to macrophage-colony-stimulating factor (MCSF) to induce macrophage properties, before activation of inflammatory pathways using <i>E. coli</i> lipopolysaccharide (LPS). Under all culture conditions, a significant amount of endogenously synthesized HA localized in LAMP1-positive lysosomal vesicles. However, this intracellular pool was depleted after the addition of exogenous HMW HA and was accompanied by enhanced proteolytic processing and secretion of de novo synthesized versican, much of which was associated with endosomal compartments. No changes were detected in synthesis, secretion, or proteolytic processing of aggrecan or lubricin (PRG4). The addition of HMW HA also modulated a range of LPS-affected genes in the TLR signaling and phagocytosis pathways, as well as endogenous HA metabolism genes, such as <i>Has1</i>, <i>Hyal1</i>, <i>Hyal2</i>, and <i>Tmem2</i>. However, there was no evidence for association of endogenous or exogenous HMW HA with cell surface CD44, TLR2 or TLR4 protein, suggesting that its physiochemical effects on pericelluar pH and/or ionic strength might be the primary modulators of signal transduction and vesicular trafficking by this cell type. We discuss the implications of these findings in terms of a potential in vivo effect of therapeutically applied HMW HA on the modification of osteoarthritis-related joint pathologies, such as pro-inflammatory and degradative responses of multipotent mesenchymal cells residing in the synovial membrane, the underlying adipose tissue, and the articular cartilage surface. |
| first_indexed | 2024-03-10T18:30:59Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:30:59Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d1aac4de730d49b78fe68196ed1166712023-11-20T06:37:55ZengMDPI AGCells2073-44092020-07-0197168110.3390/cells9071681Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of VersicanJiapeng Xue0Jinnan Chen1Quan Shen2Deva Chan3Jun Li4Adam P. Tanguay5Tannin A. Schmidt6Faizan Niazi7Anna Plaas8Department of Internal Medicine (Division of Rheumatology), Rush University Medical Center, Chicago, IL 60612, USADepartment of Internal Medicine (Division of Rheumatology), Rush University Medical Center, Chicago, IL 60612, USADepartment of Neurosurgery, Rush University Medical Center, Chicago, IL 60612, USADepartment of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USADepartment of Internal Medicine (Division of Rheumatology), Rush University Medical Center, Chicago, IL 60612, USABiomedical Engineering Department, University of Connecticut Health Center, Farmington, CT 06030, USABiomedical Engineering Department, University of Connecticut Health Center, Farmington, CT 06030, USAFerring Pharmaceuticals Inc., Parsippany, NJ 07054, USADepartment of Internal Medicine (Division of Rheumatology), Rush University Medical Center, Chicago, IL 60612, USAWe have examined the effect of exogenous linear chain high molecular weight hyaluronic acid (HMW HA) on endogenously synthesized hyaluronic acid (HA) and associated binding proteins in primary cultures of fibroblast-like stromal cells that were obtained by collagenase digestion of the murine peripatellar fat pad. The cultures were expanded in DMEM that was supplemented with fetal bovine serum and basic fibroblast growth factor (bFGF) then exposed to macrophage-colony-stimulating factor (MCSF) to induce macrophage properties, before activation of inflammatory pathways using <i>E. coli</i> lipopolysaccharide (LPS). Under all culture conditions, a significant amount of endogenously synthesized HA localized in LAMP1-positive lysosomal vesicles. However, this intracellular pool was depleted after the addition of exogenous HMW HA and was accompanied by enhanced proteolytic processing and secretion of de novo synthesized versican, much of which was associated with endosomal compartments. No changes were detected in synthesis, secretion, or proteolytic processing of aggrecan or lubricin (PRG4). The addition of HMW HA also modulated a range of LPS-affected genes in the TLR signaling and phagocytosis pathways, as well as endogenous HA metabolism genes, such as <i>Has1</i>, <i>Hyal1</i>, <i>Hyal2</i>, and <i>Tmem2</i>. However, there was no evidence for association of endogenous or exogenous HMW HA with cell surface CD44, TLR2 or TLR4 protein, suggesting that its physiochemical effects on pericelluar pH and/or ionic strength might be the primary modulators of signal transduction and vesicular trafficking by this cell type. We discuss the implications of these findings in terms of a potential in vivo effect of therapeutically applied HMW HA on the modification of osteoarthritis-related joint pathologies, such as pro-inflammatory and degradative responses of multipotent mesenchymal cells residing in the synovial membrane, the underlying adipose tissue, and the articular cartilage surface.https://www.mdpi.com/2073-4409/9/7/1681osteoarthritissynoviumstromal cellsaggrecanversicanPRG4 |
| spellingShingle | Jiapeng Xue Jinnan Chen Quan Shen Deva Chan Jun Li Adam P. Tanguay Tannin A. Schmidt Faizan Niazi Anna Plaas Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican Cells osteoarthritis synovium stromal cells aggrecan versican PRG4 |
| title | Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican |
| title_full | Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican |
| title_fullStr | Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican |
| title_full_unstemmed | Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican |
| title_short | Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican |
| title_sort | addition of high molecular weight hyaluronic acid to fibroblast like stromal cells modulates endogenous hyaluronic acid metabolism and enhances proteolytic processing and secretion of versican |
| topic | osteoarthritis synovium stromal cells aggrecan versican PRG4 |
| url | https://www.mdpi.com/2073-4409/9/7/1681 |
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