Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritis
Articular cartilage may regenerate poorly after injury or during aging. In vitro, farnesol can modulate extracellular matrix synthesis and restore chondrocyte phenotypes by increasing type II collagen (COL II) and glycosaminoglycan (GAG) production. Here, we evaluated farnesol's preventive and...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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AIP Publishing LLC
2023-03-01
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| Series: | APL Bioengineering |
| Online Access: | http://dx.doi.org/10.1063/5.0129530 |
| _version_ | 1827893524290338816 |
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| author | Chun Yu Chen Shyh Ming Kuo Guan Xuan Wu Shan Wei Yang |
| author_facet | Chun Yu Chen Shyh Ming Kuo Guan Xuan Wu Shan Wei Yang |
| author_sort | Chun Yu Chen |
| collection | DOAJ |
| description | Articular cartilage may regenerate poorly after injury or during aging. In vitro, farnesol can modulate extracellular matrix synthesis and restore chondrocyte phenotypes by increasing type II collagen (COL II) and glycosaminoglycan (GAG) production. Here, we evaluated farnesol's preventive and reparative effects against osteoarthritis (OA) in vivo. We induced OA in rabbits through resection of the lateral collateral ligament and meniscus. After 2 weeks, the affected limb was treated with 0.5 ml of 0.4 mM farnesol, hyaluronan (HA) nanoparticle-encapsulated 0.8 mM farnesol (Farn/HA), or HA nanoparticles intra-articularly. After 2 and 6 treatment weeks, synovial inflammatory cytokine levels were analyzed. We also removed the entire joint cartilage from lateral femoral condyles for histological investigation. The half-maximum inhibitory concentration of farnesol was 0.5 mM. Farn/HA had relatively low cytotoxicity showing cells remained viable after being treated with 1 mM a concentration Farn/HA. Untreated lateral condyle exhibited extensive wear. By contrast, 0.4 mM farnesol or 0.8 mM Farn/HA led to a relatively transparent and bright appearance. After 2 and 6 treatment weeks, farnesol, particularly 0.8 mM Farn/HA, reduced matrix metalloproteinase 1 and 13 levels considerably. Therefore, 0.8 mM Farn/HA, which enabled slow drug release, demonstrated the highest anti-inflammatory and OA preventive effects. After 6 treatment weeks, farnesol also promoted COL II and GAG synthesis and, thus, aided healing. |
| first_indexed | 2024-03-12T21:53:58Z |
| format | Article |
| id | doaj.art-45cfb96888c3482a9b365d3be45e324e |
| institution | Directory Open Access Journal |
| issn | 2473-2877 |
| language | English |
| last_indexed | 2024-03-12T21:53:58Z |
| publishDate | 2023-03-01 |
| publisher | AIP Publishing LLC |
| record_format | Article |
| series | APL Bioengineering |
| spelling | doaj.art-45cfb96888c3482a9b365d3be45e324e2023-07-25T19:45:11ZengAIP Publishing LLCAPL Bioengineering2473-28772023-03-0171016105016105-1310.1063/5.0129530Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritisChun Yu Chen0Shyh Ming Kuo1Guan Xuan Wu2Shan Wei Yang3 Department of Electrical Engineering, I-Shou University, Kaohsiung City, Taiwan Department of Biomedical Engineering, I-Shou University, Kaohsiung City, Taiwan Department of Biomedical Engineering, I-Shou University, Kaohsiung City, Taiwan Department of Orthopedics, Kaohsiung Veterans General Hospital, Kaohsiung Veterans General Hospital, Kaohsiung City 81346, TaiwanArticular cartilage may regenerate poorly after injury or during aging. In vitro, farnesol can modulate extracellular matrix synthesis and restore chondrocyte phenotypes by increasing type II collagen (COL II) and glycosaminoglycan (GAG) production. Here, we evaluated farnesol's preventive and reparative effects against osteoarthritis (OA) in vivo. We induced OA in rabbits through resection of the lateral collateral ligament and meniscus. After 2 weeks, the affected limb was treated with 0.5 ml of 0.4 mM farnesol, hyaluronan (HA) nanoparticle-encapsulated 0.8 mM farnesol (Farn/HA), or HA nanoparticles intra-articularly. After 2 and 6 treatment weeks, synovial inflammatory cytokine levels were analyzed. We also removed the entire joint cartilage from lateral femoral condyles for histological investigation. The half-maximum inhibitory concentration of farnesol was 0.5 mM. Farn/HA had relatively low cytotoxicity showing cells remained viable after being treated with 1 mM a concentration Farn/HA. Untreated lateral condyle exhibited extensive wear. By contrast, 0.4 mM farnesol or 0.8 mM Farn/HA led to a relatively transparent and bright appearance. After 2 and 6 treatment weeks, farnesol, particularly 0.8 mM Farn/HA, reduced matrix metalloproteinase 1 and 13 levels considerably. Therefore, 0.8 mM Farn/HA, which enabled slow drug release, demonstrated the highest anti-inflammatory and OA preventive effects. After 6 treatment weeks, farnesol also promoted COL II and GAG synthesis and, thus, aided healing.http://dx.doi.org/10.1063/5.0129530 |
| spellingShingle | Chun Yu Chen Shyh Ming Kuo Guan Xuan Wu Shan Wei Yang Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritis APL Bioengineering |
| title | Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritis |
| title_full | Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritis |
| title_fullStr | Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritis |
| title_full_unstemmed | Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritis |
| title_short | Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritis |
| title_sort | synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection induced osteoarthritis |
| url | http://dx.doi.org/10.1063/5.0129530 |
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