The intra-articular injection of RANKL-binding peptides inhibits cartilage degeneration in a murine model of osteoarthritis
| Autor: | Yukihiko Tamura, Ramachandran Murali, Kazuhiro Aoki, Yasuhiko Tabata, Yuki Yoshinari, Md. Zahirul Haque Bhuyan, Eri Sone, Chizuko Maeda, Mariko Takahashi, Yoshihiro Waki |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases Cartilage Articular Male Peptide Osteoarthritis Bone and Bones Cell Line Injections Intra-Articular 03 medical and health sciences 0302 clinical medicine Cartilage repair Chondrocytes Mesenchymal cell proliferation medicine Animals Humans Receptor Cell Proliferation 030203 arthritis & rheumatology Pharmacology chemistry.chemical_classification Osteoblasts biology Chemistry Cartilage Mesenchymal stem cell lcsh:RM1-950 RANK Ligand Osteoblast Cell Differentiation Mesenchymal Stem Cells medicine.disease Cell biology Iodoacetic Acid Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology RANKL Immunology biology.protein Molecular Medicine Monosodium iodoacetate (MIA) RANKL-binding peptide Oligopeptides |
| Zdroj: | Journal of Pharmacological Sciences, Vol 134, Iss 2, Pp 124-130 (2017) |
| ISSN: | 1347-8648 |
| Popis: | We recently found that the receptor activator of NF-κB ligand (RANKL)-binding peptide, OP3-4 stimulated the differentiation of both chondrocytes and osteoblasts. OP3-4 is also shown to inhibit cartilage degeneration. To clarify whether the peptide can inhibit cartilage degeneration without stimulating bone formation, we first performed a proliferation assay using C3H10T1/2 (the murine mesenchymal stem cell line), which is the common origin of both chondrocytes and osteoblasts. The RANKL-binding peptides, OP3-4 and W9, promoted cellular proliferation at 24 and 48 h, respectively. Next, we injected both peptides into the intra-articular space of the knee joints of mice with monosodium-iodoacetate (MIA)-induced osteoarthritis to clarify the effects of the peptides on cartilage tissue. Twenty-five nine-week-old male C57BL/6J mice received injections of vehicle, or the same molar amount of W9, OP3-4, or a control peptide (which could not stimulate osteoblast differentiation) on days 7, 14, and 21 after the injection of MIA. The mice were sacrificed on day 28. The histomorphometric analyses revealed that both peptides inhibited the degeneration of cartilage without enhancing bone formation activity. Our data suggest that the stimulation of mesenchymal cell proliferation by the RANKL-binding peptides might lead to the inhibition of cartilage degeneration. |
| Databáze: | OpenAIRE |
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