Secreted Frizzled‐related proteins (sFRPs) in osteo‐articular diseases: much more than simple antagonists of Wnt signaling?

Osteo‐articular diseases are characterized by a dysregulation of joint and/or bone homeostasis. These include diseases affecting the joints originally, such as osteoarthritis and rheumatoid arthritis, or the bone, such as osteoporosis. Inflammation and the involvement of Wingless‐related integration...

Full description

Saved in:

Bibliographic Details
Published in:	The FEBS journal 2019-12, Vol.286 (24), p.4832-4851
Main Authors:	Claudel, Marion, Jouzeau, Jean‐Yves, Cailotto, Frédéric
Format:	Article
Language:	eng
Subjects:	Arthritis Biochemistry, Molecular Biology Biomedical materials Bone remodelling Bone turnover Cell activation Cell membranes Diseases Embryos Extracellular matrix Frizzled protein Glycoproteins Homeostasis Human health and pathology Immune system Inflammation Inflammatory response Joint diseases Joints (anatomy) Life Sciences Matrix metalloproteinase Matrix metalloproteinases Osteoarthritis Osteoporosis osteo‐articular diseases Pathways Proteins Receptors Rheumatoid arthritis Rhumatology and musculoskeletal system secreted Frizzled‐related proteins Signal transduction Signaling Thrombospondin Tissue engineering Wnt Wnt protein
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Osteo‐articular diseases are characterized by a dysregulation of joint and/or bone homeostasis. These include diseases affecting the joints originally, such as osteoarthritis and rheumatoid arthritis, or the bone, such as osteoporosis. Inflammation and the involvement of Wingless‐related integration site (Wnt) signaling pathways are key pathophysiological features of these diseases resulting in tissue degradation by matrix‐degrading enzymes, namely matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTs), secreted by the joint resident cells and/or by infiltrating immune cells. Activation of Wnt signaling pathways is modulated by different families of proteins, including Dickkopfs and the secreted Frizzled‐related proteins (sFRPs). The sFRP family is composed of five secreted glycoproteins in mammals that regulate Wnt signaling in the extracellular compartment. Indeed, sFRPs are able to bind both to the soluble Wnt ligands and to their cell membrane receptors, the Frizzled proteins. Their expression profile is altered in osteo‐articular diseases, suggesting that they could account for the abnormal activation of Wnt pathways. In the present article, we review how sFRPs are more than simple antagonists of the Wnt signaling pathways and discuss their pathophysiological relevance in the context of osteo‐articular diseases. We detail their Wnt‐dependent and their Wnt‐independent roles, with a particular emphasis on their ability to modulate the inflammatory response and extracellular matrix (ECM) remodeling. We also discuss their potential therapeutic use with a focus on bone remodeling, osteo‐articular cancers, and tissue engineering. Osteo‐articular diseases are characterized by a dysregulation of joint homeostasis. Alterations in Wingless‐related integration site (Wnt) pathways are key pathophysiological features of these diseases. Wnt pathways are modulated by the secreted Frizzled‐related proteins (sFRPs). Their expression profile is altered in osteo‐articular diseases, suggesting their involvement in abnormal Wnt pathways activation. We review how sFRPs are more than Wnt pathways antagonists, and discuss their pathophysiological relevance in osteo‐articular diseases.
ISSN:	1742-464X 1742-4658