Hyaluronan suppresses enhanced cathepsin K expression via activation of NF-κB with mechanical stress loading in a human chondrocytic HCS-2/8 cells
Cathepsin K is a protease known to be involved in not only bone remodeling and resorption, but also articular cartilage degradation that leads to osteoarthritis (OA). Hyaluronan (HA) plays a pivotal role in maintaining homeostasis within articular chondrocytes. Intra-articular supplementation of hig...
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Published in | Scientific reports Vol. 10; no. 1; p. 216 |
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Main Authors | , , , , , , , |
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Abstract | Cathepsin K is a protease known to be involved in not only bone remodeling and resorption, but also articular cartilage degradation that leads to osteoarthritis (OA). Hyaluronan (HA) plays a pivotal role in maintaining homeostasis within articular chondrocytes. Intra-articular supplementation of high molecular weight hyaluronan (HMW-HA) has been widely used in OA treatment. However, its prospective mechanism of action is still unclear. In this study, we examined the suppressive effect of HA on enhanced cathepsin K expression induced by mechanical stress loading. A human chondrocytic HCS-2/8 cells were cultured in silicon chambers and subjected to cyclic tensile stress (CTS) loading. CTS loading significantly increased messenger ribonucleic acid and protein expression of cathepsin K, which appeared to be suppressed by pre-treatment with HMW-HA. Activation of nuclear factor-kappa B (NF-κB) was induced by CTS loading, and suppressed by pre-treatment with HMW-HA. Helenalin, a chemical inhibitor of NF-κB, clearly suppressed the enhanced expression of cathepsin K, as well as NF-κB activation induced by CTS loading. The suppressive effect of HMW-HA on enhanced cathepsin K expression via NF-κB inhibition impacts the effectiveness of HMW-HA in OA treatment. Our findings provide new evidence supporting the biological effectiveness of intra-articular HMW-HA injections for treatment of OA. |
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AbstractList | Cathepsin K is a protease known to be involved in not only bone remodeling and resorption, but also articular cartilage degradation that leads to osteoarthritis (OA). Hyaluronan (HA) plays a pivotal role in maintaining homeostasis within articular chondrocytes. Intra-articular supplementation of high molecular weight hyaluronan (HMW-HA) has been widely used in OA treatment. However, its prospective mechanism of action is still unclear. In this study, we examined the suppressive effect of HA on enhanced cathepsin K expression induced by mechanical stress loading. A human chondrocytic HCS-2/8 cells were cultured in silicon chambers and subjected to cyclic tensile stress (CTS) loading. CTS loading significantly increased messenger ribonucleic acid and protein expression of cathepsin K, which appeared to be suppressed by pre-treatment with HMW-HA. Activation of nuclear factor-kappa B (NF-κB) was induced by CTS loading, and suppressed by pre-treatment with HMW-HA. Helenalin, a chemical inhibitor of NF-κB, clearly suppressed the enhanced expression of cathepsin K, as well as NF-κB activation induced by CTS loading. The suppressive effect of HMW-HA on enhanced cathepsin K expression via NF-κB inhibition impacts the effectiveness of HMW-HA in OA treatment. Our findings provide new evidence supporting the biological effectiveness of intra-articular HMW-HA injections for treatment of OA. Abstract Cathepsin K is a protease known to be involved in not only bone remodeling and resorption, but also articular cartilage degradation that leads to osteoarthritis (OA). Hyaluronan (HA) plays a pivotal role in maintaining homeostasis within articular chondrocytes. Intra-articular supplementation of high molecular weight hyaluronan (HMW-HA) has been widely used in OA treatment. However, its prospective mechanism of action is still unclear. In this study, we examined the suppressive effect of HA on enhanced cathepsin K expression induced by mechanical stress loading. A human chondrocytic HCS-2/8 cells were cultured in silicon chambers and subjected to cyclic tensile stress (CTS) loading. CTS loading significantly increased messenger ribonucleic acid and protein expression of cathepsin K, which appeared to be suppressed by pre-treatment with HMW-HA. Activation of nuclear factor-kappa B (NF-κB) was induced by CTS loading, and suppressed by pre-treatment with HMW-HA. Helenalin, a chemical inhibitor of NF-κB, clearly suppressed the enhanced expression of cathepsin K, as well as NF-κB activation induced by CTS loading. The suppressive effect of HMW-HA on enhanced cathepsin K expression via NF-κB inhibition impacts the effectiveness of HMW-HA in OA treatment. Our findings provide new evidence supporting the biological effectiveness of intra-articular HMW-HA injections for treatment of OA. |
ArticleNumber | 216 |
Author | Ishiguro, Naoki Kishimoto, Kenji Hattori, Kyosuke Kojima, Toshihisa Suzuki, Mochihito Takahashi, Nobunori Sobue, Yasumori Ohashi, Yoshifumi |
Author_xml | – sequence: 1 givenname: Mochihito orcidid: 0000-0003-4895-5028 surname: Suzuki fullname: Suzuki, Mochihito organization: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine – sequence: 2 givenname: Nobunori surname: Takahashi fullname: Takahashi, Nobunori email: nobunori@med.nagoya-u.ac.jp organization: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine – sequence: 3 givenname: Yasumori surname: Sobue fullname: Sobue, Yasumori organization: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine – sequence: 4 givenname: Yoshifumi surname: Ohashi fullname: Ohashi, Yoshifumi organization: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine – sequence: 5 givenname: Kenji surname: Kishimoto fullname: Kishimoto, Kenji organization: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine – sequence: 6 givenname: Kyosuke surname: Hattori fullname: Hattori, Kyosuke organization: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine – sequence: 7 givenname: Naoki surname: Ishiguro fullname: Ishiguro, Naoki organization: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine – sequence: 8 givenname: Toshihisa surname: Kojima fullname: Kojima, Toshihisa organization: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine |
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CitedBy_id | crossref_primary_10_3390_ijms21093140 crossref_primary_10_1007_s00264_021_04938_1 crossref_primary_10_1152_ajpcell_00464_2022 crossref_primary_10_1016_j_cellsig_2022_110531 crossref_primary_10_1016_j_arr_2021_101315 crossref_primary_10_3389_fcell_2020_00433 crossref_primary_10_3389_fcell_2022_818462 |
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Snippet | Cathepsin K is a protease known to be involved in not only bone remodeling and resorption, but also articular cartilage degradation that leads to... Abstract Cathepsin K is a protease known to be involved in not only bone remodeling and resorption, but also articular cartilage degradation that leads to... |
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SubjectTerms | 38/77 692/4017 692/4023/808 82/1 Adjuvants, Immunologic - pharmacology Arthritis Bone remodeling Bone resorption Bone surgery Cartilage Cartilage (articular) Cartilage diseases Cartilage, Articular - cytology Cartilage, Articular - drug effects Cartilage, Articular - metabolism Cathepsin K Cathepsin K - genetics Cathepsin K - metabolism Cells, Cultured Chondrocytes Chondrocytes - cytology Chondrocytes - drug effects Chondrocytes - metabolism Collagen Gene Expression Regulation - drug effects Homeostasis Humanities and Social Sciences Humans Hyaluronan Receptors - genetics Hyaluronan Receptors - metabolism Hyaluronic acid Hyaluronic Acid - pharmacology Loading Molecular weight multidisciplinary NF-kappa B - genetics NF-kappa B - metabolism NF-κB protein Osteoarthritis Phosphorylation Protein expression Proteins Science Science (multidisciplinary) Signal Transduction Stress, Mechanical Supplements |
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Title | Hyaluronan suppresses enhanced cathepsin K expression via activation of NF-κB with mechanical stress loading in a human chondrocytic HCS-2/8 cells |
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