Fat-cartilage axis: the regulation of IL-6/Osteopontin signaling in osteoarthritis of mice
Abstract The infrapatellar fat pad (IPFP) acts as a bioactive reservoir, secreting proinflammatory cytokines that orchestrate both local and systemic inflammatory cascades. Despite its emerging role in knee osteoarthritis (OA) pathophysiology, the molecular and cellular mechanisms driving IPFP-media...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02622-6 |
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| author | Bing-yang Dai Zhong-lian Huang Ming-gui Bao Hong-jiang Chen Xiao-hui Lu Jun Hu |
| author_facet | Bing-yang Dai Zhong-lian Huang Ming-gui Bao Hong-jiang Chen Xiao-hui Lu Jun Hu |
| author_sort | Bing-yang Dai |
| collection | DOAJ |
| description | Abstract The infrapatellar fat pad (IPFP) acts as a bioactive reservoir, secreting proinflammatory cytokines that orchestrate both local and systemic inflammatory cascades. Despite its emerging role in knee osteoarthritis (OA) pathophysiology, the molecular and cellular mechanisms driving IPFP-mediated disease progression remain a critical gap in mechanistic understanding. 12-week-old male C57BL/6 mice underwent either destabilization of the medial meniscus (DMM) surgery or Sham surgery. Here, we find that the extreme sensitivity of IPFP makes it prone to act as a reservoir of inflammatory factors, which may indiscriminately disrupt the stability of its surrounding tissues. We further ascertain the role of IL-6 in initializing fibrosis in IPFP at early stage of OA and modulating osteopontin (OPN) secretion that cascades cartilage deterioration. Notably, removal of the IPFP in DMM mice reverses the abnormal functions of the knee joint. Compromising the progress of fibrosis by intra-IPFP injection of siRNA Cd61 or inhibition of OPN expression can drastically ameliorate cartilage deterioration. Our findings elucidate a pivotal role for IL-6 in instigating fibrotic remodeling within the IPFP during early-stage OA, concurrently regulating OPN secretion to propagate cartilage matrix degradation. This study thus establishes a conceptual framework for therapeutic intervention by targeting the IL-6/OPN signaling axis in the IPFP during OA initiation, offering a promising strategy to disrupt disease progression. |
| format | Article |
| id | doaj-art-5d4fef5aaf474ba6b3797a873931d8d9 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-5d4fef5aaf474ba6b3797a873931d8d92025-08-20T03:42:26ZengNature Publishing GroupCell Death Discovery2058-77162025-07-0111111210.1038/s41420-025-02622-6Fat-cartilage axis: the regulation of IL-6/Osteopontin signaling in osteoarthritis of miceBing-yang Dai0Zhong-lian Huang1Ming-gui Bao2Hong-jiang Chen3Xiao-hui Lu4Jun Hu5Department of Orthopaedics, The First Affiliated Hospital of Shantou University Medical CollegeDepartment of Orthopaedics, The First Affiliated Hospital of Shantou University Medical CollegeDepartment of Orthopaedics, The First Affiliated Hospital of Shantou University Medical CollegeDepartment of Orthopaedics, The First Affiliated Hospital of Shantou University Medical CollegeDepartment of Orthopaedics, The First Affiliated Hospital of Shantou University Medical CollegeDepartment of Orthopaedics, The First Affiliated Hospital of Shantou University Medical CollegeAbstract The infrapatellar fat pad (IPFP) acts as a bioactive reservoir, secreting proinflammatory cytokines that orchestrate both local and systemic inflammatory cascades. Despite its emerging role in knee osteoarthritis (OA) pathophysiology, the molecular and cellular mechanisms driving IPFP-mediated disease progression remain a critical gap in mechanistic understanding. 12-week-old male C57BL/6 mice underwent either destabilization of the medial meniscus (DMM) surgery or Sham surgery. Here, we find that the extreme sensitivity of IPFP makes it prone to act as a reservoir of inflammatory factors, which may indiscriminately disrupt the stability of its surrounding tissues. We further ascertain the role of IL-6 in initializing fibrosis in IPFP at early stage of OA and modulating osteopontin (OPN) secretion that cascades cartilage deterioration. Notably, removal of the IPFP in DMM mice reverses the abnormal functions of the knee joint. Compromising the progress of fibrosis by intra-IPFP injection of siRNA Cd61 or inhibition of OPN expression can drastically ameliorate cartilage deterioration. Our findings elucidate a pivotal role for IL-6 in instigating fibrotic remodeling within the IPFP during early-stage OA, concurrently regulating OPN secretion to propagate cartilage matrix degradation. This study thus establishes a conceptual framework for therapeutic intervention by targeting the IL-6/OPN signaling axis in the IPFP during OA initiation, offering a promising strategy to disrupt disease progression.https://doi.org/10.1038/s41420-025-02622-6 |
| spellingShingle | Bing-yang Dai Zhong-lian Huang Ming-gui Bao Hong-jiang Chen Xiao-hui Lu Jun Hu Fat-cartilage axis: the regulation of IL-6/Osteopontin signaling in osteoarthritis of mice Cell Death Discovery |
| title | Fat-cartilage axis: the regulation of IL-6/Osteopontin signaling in osteoarthritis of mice |
| title_full | Fat-cartilage axis: the regulation of IL-6/Osteopontin signaling in osteoarthritis of mice |
| title_fullStr | Fat-cartilage axis: the regulation of IL-6/Osteopontin signaling in osteoarthritis of mice |
| title_full_unstemmed | Fat-cartilage axis: the regulation of IL-6/Osteopontin signaling in osteoarthritis of mice |
| title_short | Fat-cartilage axis: the regulation of IL-6/Osteopontin signaling in osteoarthritis of mice |
| title_sort | fat cartilage axis the regulation of il 6 osteopontin signaling in osteoarthritis of mice |
| url | https://doi.org/10.1038/s41420-025-02622-6 |
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