ReferenceID 5217
Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways
Arthritis Res Ther
BACKGROUND: To investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium during osteoarthritis (O
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- Reference Id
- 5217
- Evidence Id
- 21807
- Core Evidence Id
- 21807
- Source Reference Id
- 3710
- Herb2 Reference Id
- HBREF004507
- Subject Paper Key
- HBIN026367_33990219
- Pubmed Id
- 33990219
- Doi
- 10.1186/s13075-021-02512-z
- Paper Title
- Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways
- Paper Abstract
- BACKGROUND: To investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium during osteoarthritis (OA) development. METHODS: Ten-week-old male C57BL/6 mice were randomized and assigned to vehicle, collagenase-induced OA (CIOA), or CIOA with intra-articular fargesin treatment groups. Articular cartilage degeneration was evaluated using the Osteoarthritis Research Society International (OARSI) score. Immunostaining and western blot analyses were conducted to detect relative protein. Raw264.7 cells were treated with LPS or IL-4 to investigate the role of polarized macrophages. ADTC5 cells were treated with IL-1beta and conditioned medium was collected to investigate the crosstalk between chondrocytes and macrophages. RESULTS: Fargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by downregulation of IL-6 and IL-1beta and upregulation of IL-10 in serum. Conditioned medium (CM) from M1 macrophages treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen and increased Col2a1 and SOX9 in OA chondrocytes, but fargesin alone did not affect chondrocyte catabolic processes. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-kappaB signaling. CONCLUSIONS: This study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by downregulating p38/ERK MAPK and p65/NF-kappaB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.
- Journal
- Arthritis Res Ther
- Publish Year
- 2021
- Experiment Subject
- mouse; adtc5 cells; raw264.7 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Synovitis; Osteoarthritis; Fargesin Attenuated Articular Cartilage Degeneration; Cartilage Degeneration; Articular Cartilage Degeneration
- Paper Title Cn
- Paper Title En
- Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways
- Bilingual Status
- semi_complete