Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis
Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, t...
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2024-12-01
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| author | Hyun-Joo Lee Dae-Yong Kim Hyeon jeong Noh Song Yi Lee Ji Ae Yoo Samuel Jaeyoon Won Yoon Sang Jeon Ji Hoon Baek Dong Jin Ryu |
| author_facet | Hyun-Joo Lee Dae-Yong Kim Hyeon jeong Noh Song Yi Lee Ji Ae Yoo Samuel Jaeyoon Won Yoon Sang Jeon Ji Hoon Baek Dong Jin Ryu |
| author_sort | Hyun-Joo Lee |
| collection | DOAJ |
| description | Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA. Autologous ASCs were isolated from the stromal vascular fraction (SVF) of adipose tissue obtained from 22 OA patients. The isolated ASCs were cultured and characterized using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to the phenotype and immune regulatory factors of MSCs. Based on IL-6 expression levels, ASCs were divided into high and low IL-6 expression groups. These groups were then co-cultured with activated peripheral blood mononuclear cells (PBMCs) to evaluate their immune-modulatory capacity, including the induction of regulatory T cells, inhibition of immune cell proliferation, and regulation of key cytokines, such as interferon-gamma (IFN-γ). Additionally, RANKL expression, a critical factor in osteoclastogenesis and cartilage degradation, was assessed in both ASC groups. High IL-6-expressing ASCs demonstrated a significantly greater capacity to inhibit immune cell proliferation and IFN-γ production compared to their low IL-6-expressing counterparts under co-culture conditions. Moreover, the group of ASCs with high IL-6 expression showed a marked reduction in RANKL expression, suggesting enhanced potential to control osteoclast activity and subsequent cartilage defect in OA. Conclusion: Autologous ASCs with elevated IL-6 expression exhibit enhanced immunomodulatory properties, particularly in regulating over-activated immune response and reducing osteoclastogenesis through RANKL suppression. These findings indicate that selecting ASCs based on IL-6 expression could enhance the therapeutic efficacy of ASC-based treatments for OA by mitigating immune-driven joint inflammation and cartilage degradation, potentially slowing disease progression. |
| format | Article |
| id | doaj-art-90f4c92bf9fd4cccbb06fa65cfec1a9b |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-90f4c92bf9fd4cccbb06fa65cfec1a9b2025-08-20T02:53:19ZengMDPI AGCells2073-44092024-12-011324204610.3390/cells13242046Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in OsteoarthritisHyun-Joo Lee0Dae-Yong Kim1Hyeon jeong Noh2Song Yi Lee3Ji Ae Yoo4Samuel Jaeyoon Won5Yoon Sang Jeon6Ji Hoon Baek7Dong Jin Ryu8Stem Cell R&D Center, N-BIOTEK, Inc., 104-706, Technopark Ssangyong 3Cha, 397, Seokcheon-ro, Bucheon-si 14449, Republic of KoreaStem Cell R&D Center, N-BIOTEK, Inc., 104-706, Technopark Ssangyong 3Cha, 397, Seokcheon-ro, Bucheon-si 14449, Republic of KoreaStem Cell R&D Center, N-BIOTEK, Inc., 104-706, Technopark Ssangyong 3Cha, 397, Seokcheon-ro, Bucheon-si 14449, Republic of KoreaStem Cell R&D Center, N-BIOTEK, Inc., 104-706, Technopark Ssangyong 3Cha, 397, Seokcheon-ro, Bucheon-si 14449, Republic of KoreaStem Cell R&D Center, N-BIOTEK, Inc., 104-706, Technopark Ssangyong 3Cha, 397, Seokcheon-ro, Bucheon-si 14449, Republic of KoreaOrthopedic Surgery, Inha University Hospital, Incheon 22332, Republic of KoreaOrthopedic Surgery, Inha University Hospital, Incheon 22332, Republic of KoreaOrthopedic Surgery, Inha University Hospital, Incheon 22332, Republic of KoreaOrthopedic Surgery, Inha University Hospital, Incheon 22332, Republic of KoreaInterleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA. Autologous ASCs were isolated from the stromal vascular fraction (SVF) of adipose tissue obtained from 22 OA patients. The isolated ASCs were cultured and characterized using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to the phenotype and immune regulatory factors of MSCs. Based on IL-6 expression levels, ASCs were divided into high and low IL-6 expression groups. These groups were then co-cultured with activated peripheral blood mononuclear cells (PBMCs) to evaluate their immune-modulatory capacity, including the induction of regulatory T cells, inhibition of immune cell proliferation, and regulation of key cytokines, such as interferon-gamma (IFN-γ). Additionally, RANKL expression, a critical factor in osteoclastogenesis and cartilage degradation, was assessed in both ASC groups. High IL-6-expressing ASCs demonstrated a significantly greater capacity to inhibit immune cell proliferation and IFN-γ production compared to their low IL-6-expressing counterparts under co-culture conditions. Moreover, the group of ASCs with high IL-6 expression showed a marked reduction in RANKL expression, suggesting enhanced potential to control osteoclast activity and subsequent cartilage defect in OA. Conclusion: Autologous ASCs with elevated IL-6 expression exhibit enhanced immunomodulatory properties, particularly in regulating over-activated immune response and reducing osteoclastogenesis through RANKL suppression. These findings indicate that selecting ASCs based on IL-6 expression could enhance the therapeutic efficacy of ASC-based treatments for OA by mitigating immune-driven joint inflammation and cartilage degradation, potentially slowing disease progression.https://www.mdpi.com/2073-4409/13/24/2046autologous adipose-derived stem cell (ASCs)osteoarthritis (OA)interleukin-6 (IL-6)receptor activator of nuclear factor kappa-Β ligand (RANKL) |
| spellingShingle | Hyun-Joo Lee Dae-Yong Kim Hyeon jeong Noh Song Yi Lee Ji Ae Yoo Samuel Jaeyoon Won Yoon Sang Jeon Ji Hoon Baek Dong Jin Ryu Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis Cells autologous adipose-derived stem cell (ASCs) osteoarthritis (OA) interleukin-6 (IL-6) receptor activator of nuclear factor kappa-Β ligand (RANKL) |
| title | Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis |
| title_full | Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis |
| title_fullStr | Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis |
| title_full_unstemmed | Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis |
| title_short | Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis |
| title_sort | elevated il 6 expression in autologous adipose derived stem cells regulates rankl mediated inflammation in osteoarthritis |
| topic | autologous adipose-derived stem cell (ASCs) osteoarthritis (OA) interleukin-6 (IL-6) receptor activator of nuclear factor kappa-Β ligand (RANKL) |
| url | https://www.mdpi.com/2073-4409/13/24/2046 |
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