RRC ID 74457
Author Furuya Y, Mera H, Itokazu M, Terai S, Nakamura H, Wakitani S, Yasuda H.
Title Induction of chondrogenesis with a RANKL-binding peptide, WP9QY, in vitro and in vivo in a rabbit model.
Journal Biochem Biophys Res Commun
Abstract WP9QY (W9) is a receptor activator of nuclear factor-κB ligand (RANKL)-binding peptide that inhibits osteoclastogenesis by blunting the RANKL-RANK interaction, and also increases osteoblastogenesis via RANKL reverse signaling. W9 has dual effects on osteoclasts and osteoblasts; however, it is unknown whether the peptide has an effect on chondrocytes. Here, we report that W9 induces proliferation and differentiation of chondrocytes in vitro and repairs full-thickness articular cartilage defects in vivo. W9 stimulated chondrocyte differentiation in a two-dimensional (2D) culture of human mesenchymal stem cells (hMSCs), and transforming growth factor β3 (TGF-β3) showed synergistic effects with W9 on chondrogenesis. W9 enlarged the size of 3D pellet cultures of hMSCs and produced chondrocyte-specific matrices, especially in combined treatment with TGF-β3. The peptide also stimulated proliferation of hMSCs with induction of expression of chondrogenesis-related genes. Several RANKL inhibitors had no effect on chondrocytic differentiation. RANKL-knockdown experiments showed that W9 did not induce chondrogenesis through RANKL, but did induce osteoblastogenesis through RANKL. Intraarticular injection of W9 resulted in significant repair of full-thickness articular cartilage defects in rabbits. Taken together, these results suggest that W9 ameliorates the articular cartilage defects by increasing the volume of cartilaginous matrices with accompanying induction of proliferation and differentiation of chondrocytes via mechanisms independent of RANKL inhibition and RANKL reverse signaling. Since no pharmaceuticals are clinically available for treatment of cartilage damage such as osteoarthritis, our findings demonstrate the potential of W9 to address the unmet medical needs.
Volume 602
Pages 98-104
Published 2022-4-30
DOI 10.1016/j.bbrc.2022.03.019
PII S0006-291X(22)00338-2
PMID 35259590
MeSH Animals Cartilage, Articular* / metabolism Cell Differentiation Cells, Cultured Chondrocytes / metabolism Chondrogenesis* Osteoclasts / metabolism Osteogenesis Peptides / metabolism Peptides / pharmacology Rabbits Transforming Growth Factor beta3 / metabolism
IF 2.985
Human and Animal Cells 10T1/2(RCB0247)