Abstract

Osteoarthritis, a highly age-related and chronic inflammatory disorder with cartilage loss, causes patients difficultly in movement; there is no efficient and sustainable remedy for osteoarthritis currently. Although hyaluronic acid (HA) and platelet-rich plasma (PRP) have been used to alleviate osteoarthritis, the effects could be short and multiple injections might be required. To address this issue, we exploited the property of chitosan to encapsulate recombinant human epidermal growth factor and obtained microencapsulated rhEGF (Me-rhEGF). In the current study, we induced the osteoarthritis-like symptoms with monosodium iodoacetate (MIA) in rats and investigated the therapeutic effects of Me-rhEGF. Following administration of HA/Me-rhEGF in vivo, we observed that the total Mankin scores, cartilage oligomeric protein, C-telopeptide of type II collagen, IL-1β, IL-6, IL-17A, and TNF-α cytokines, nitric oxide, and prostaglandin E2 expressions were significantly inhibited. Our results also strongly indicate that individual use of HA or rhEGF slightly decreased the inflammation and restored the destructive joint structure, but was not as drastic as seen in the HA/Me-rhEGF. Moreover, HA/Me-rhEGF profoundly reduced cartilage destruction and proteoglycan loss and downregulated matrix metalloproteinase expressions. These findings reveal that the treatment of HA/Me-rhEGF could be more beneficial than the use of single HA or rhEGF in reliving osteoarthritis and demonstrate the therapeutic application of microencapsulation technology in difficult joint disorders. In essence, we believe that the Me-rhEGF could be promising for further research and development as a clinical treatment against osteoarthritis.

Highlights

  • Osteoarthritis (OA) is a chronic, inflammatory, and degenerative joint disease, resulting in progressive cartilage damage

  • Prostaglandin E2 (PGE2; Cusabio, Biotech, Wuhan, Hubei, China), proinflammatory cytokines, including IL-1β, IL-6, IL-17A, and TNF-α, and cartilage degeneration mediators, cartilage oligomeric matrix protein (COMP) (Cusabio), and c-terminal cross-linked telopeptides of type II collagen (CTX-II) (Lifespan Biosciences Corporations, Seattle, WA, USA) were determined by indicated ELISA kits. 100 μL of diluted serum (50 μL/well for prostaglandin E2 (PGE2) kit) was added to wells coated with capture antibodies and blocked with 5% BSA blocking buffer for 2 hrs followed by washing with PBS-T buffer (0.5% Tween20 in PBS), 100 μL/well biotinylated detection antibody for 1 h, and 100 μL/well Avidin-horseradish peroxidase (HRP) for 30 min at room temperature

  • We prompted to determine whether hyaluronic acid (HA), rhEGF, or HA/Me-rhEGF could elicit any protective effects to ameliorate osteoarthritic symptoms in an animal model; we utilized monosodium iodoacetate (MIA), a selective inhibitor of glyceraldehyde-3-phosphate dehydrogenase, to induce osteoarthritis-like symptoms on rats

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Summary

Research Article

Shih-Chao Lin ,1 Xiang Zhang, Shiow-Yi Chen ,3 Chi-Chien Lin ,4 and Yen-Shuo Chiu 5,6. Hyaluronic acid (HA) and platelet-rich plasma (PRP) have been used to alleviate osteoarthritis, the effects could be short and multiple injections might be required. To address this issue, we exploited the property of chitosan to encapsulate recombinant human epidermal growth factor and obtained microencapsulated rhEGF (Me-rhEGF). HA/Me-rhEGF profoundly reduced cartilage destruction and proteoglycan loss and downregulated matrix metalloproteinase expressions. Ese findings reveal that the treatment of HA/MerhEGF could be more beneficial than the use of single HA or rhEGF in reliving osteoarthritis and demonstrate the therapeutic application of microencapsulation technology in difficult joint disorders. We believe that the Me-rhEGF could be promising for further research and development as a clinical treatment against osteoarthritis

Introduction
Material and Methods
Collect Serum and joint knee samples
Results and Discussion
Safranin O
Full Text
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