RRC ID 62072
Author Haque Bhuyan MZ, Tamura Y, Sone E, Yoshinari Y, Maeda C, Takahashi M, Tabata Y, Murali R, Waki Y, Aoki K.
Title The intra-articular injection of RANKL-binding peptides inhibits cartilage degeneration in a murine model of osteoarthritis.
Journal J Pharmacol Sci
Abstract 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.
Volume 134(2)
Pages 124-130
Published 2017-6-1
DOI 10.1016/j.jphs.2017.05.008
PII S1347-8613(17)30083-X
PMID 28648299
MeSH Animals Bone and Bones / drug effects Bone and Bones / pathology Cartilage, Articular / drug effects* Cartilage, Articular / pathology Cell Differentiation / drug effects Cell Line Cell Proliferation / drug effects Chondrocytes / drug effects Chondrocytes / pathology Humans Injections, Intra-Articular Iodoacetic Acid Male Mesenchymal Stem Cells / cytology Mesenchymal Stem Cells / drug effects Mice, Inbred C57BL Oligopeptides / pharmacology Oligopeptides / therapeutic use* Osteoarthritis / chemically induced Osteoarthritis / drug therapy* Osteoarthritis / metabolism Osteoarthritis / pathology Osteoblasts / drug effects Osteoblasts / metabolism Osteoblasts / pathology RANK Ligand / metabolism*
IF 2.835
Human and Animal Cells 10T1/2(RCB0247)