scholarly journals Microencapsulated Recombinant Human Epidermal Growth Factor Ameliorates Osteoarthritis in a Murine Model

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shih-Chao Lin ◽  
Xiang Zhang ◽  
Shiow-Yi Chen ◽  
Chi-Chien Lin ◽  
Yen-Shuo Chiu

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.

1988 ◽  
Vol 77 (3) ◽  
pp. 200-207 ◽  
Author(s):  
Dong Chool Kim ◽  
Yuichi Sugiyama ◽  
Hiroaki Satoh ◽  
Tohru Fuwa ◽  
Tatsuji Iga ◽  
...  

2019 ◽  
Vol 116 (1) ◽  
pp. 193-201
Author(s):  
Wei-Ju Liao ◽  
Meng-Ying Wu ◽  
Chen-Chung Peng ◽  
Yi-Chung Tung ◽  
Ruey-Bing Yang

Abstract Aims SCUBE1 [signal peptide-CUB-epidermal growth factor (EGF) domain-containing protein 1], expressed in endothelial cells (ECs) and platelets, exists in soluble or membrane forms. We previously showed that soluble SCUBE1 is a biomarker for platelet activation and also an active participant of thrombosis. However, whether the adhesive module of its EGF-like repeats is essential and the specific contribution of SCUBE1 synthesized in ECs or platelets to thrombosis in vivo remain unclear. Methods and results We generated new mutant (Δ2) mice lacking the entire EGF-like repeats to evaluate the module’s functional importance during thrombogenesis in vivo. The Δ2 platelet-rich plasma showed markedly impaired platelet aggregation induced by agonists including adenosine diphosphate, collagen, the thrombin agonist PAR-4 peptide and the thromboxane A2 analogue U46619. Consistently, genetic ablation of the EGF-like repeats diminished arterial thrombosis and protected Δ2 mice against lethal thromboembolism. On flow chamber assay, whole blood isolated from Δ2 or wild-type (WT) mice pre-treated with blocking antibodies against the EGF-like repeats showed a significant decrease in platelet deposition and thrombus formation on collagen-coated surfaces under arterial shear rates. Moreover, we created animals expressing SCUBE1 only in ECs (S1-EC) or platelets (S1-PLT) by reciprocal bone-marrow transplantation between WT and Δ2 mice. The time of carotid arterial thrombosis induced by ferric chloride was normal in S1-PLT chimeric mice but much prolonged in S1-EC animals. Conclusions We demonstrate that platelet-derived SCUBE1 plays a critical role in arterial thrombosis via its adhesive EGF-like repeats in vivo and suggest targeting these adhesive motifs of SCUBE1 for potential anti-thrombotic strategy.


Life Sciences ◽  
1982 ◽  
Vol 31 (7) ◽  
pp. 679-683 ◽  
Author(s):  
Masahito Uchihashi ◽  
Yukio Hirata ◽  
Takuo Fujita ◽  
Shigeru Matsukura

ChemBioChem ◽  
2007 ◽  
Vol 8 (18) ◽  
pp. 2227-2232 ◽  
Author(s):  
Lars Merkel ◽  
Yuri Cheburkin ◽  
Birgit Wiltschi ◽  
Nediljko Budisa

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei-Pang Chung ◽  
Wei-Lun Huang ◽  
Wei-An Liao ◽  
Chun-Hua Hung ◽  
Chi-Wu Chiang ◽  
...  

AbstractThe prognosis of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer has considerably improved. However, no reliable treatment besides anti-HER2 strategies has been available. FTY720, a small-molecule compound used for treating refractory multiple sclerosis, has been reported to have beneficial effects against cancers. We therefore evaluated the efficacy of FTY720 in trastuzumab-resistant breast cancer cells and investigated the possible mechanism involved. This study evaluated morphological changes after FTY720 treatment. Antiproliferative WST-1 assays and LDH Cytotoxicity Assay Kits were used to determine the treatment effects of drugs, whereas Western blot analysis was used to evaluate protein expression. Apoptotic events were investigated through annexin V staining and TUNEL assays using flow cytometry. FTY720 was effective in trastuzumab-resistant breast cancer cell lines despite the presence of PIK3CA mutation. Studied on a xenograft mouse model, FTY720-treated groups had statistically significantly poorer HCC1954 xenograft growth in vivo compared with the control group. Our findings suggest that FTY720 can overcome resistance to trastuzumab therapy in patients with HER2-positive breast cancer, with FTY720 plus trastuzumab might offer even better efficacy in vitro and in vivo.


2009 ◽  
Vol 50 (6) ◽  
pp. 545-552 ◽  
Author(s):  
Seung-Hee RYU ◽  
Soo Young MOON ◽  
Youn-Joo YANG ◽  
Sun Rock MOON ◽  
Joon Pio HONG ◽  
...  

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