Wnt and the Wnt signaling pathway in bone development and disease

Abstract

Wnt signaling affects both bone modeling, which occurs during development, and bone remodeling, which is a lifelong process involving tissue renewal. Wnt signals are especially known to affect the differentiation of osteoblasts. In this review, we summarize recent advances in understanding the mechanisms of Wnt signaling, which is divided into two major branches: the canonical pathway and the noncanonical pathway. The canonical pathway is also called the Wnt/β-catenin pathway. There are two major noncanonical pathways: the Wnt-planar cell polarity pathway (Wnt-PCP pathway) and the Wnt-calcium pathway (Wnt-Ca2+ pathway). This review also discusses how Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists affect both the bone modeling and bone remodeling processes. We also review the role of Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists in bone as demonstrated in mouse models. Disrupted Wnt signaling is linked to several bone diseases, including osteoporosis, van Buchem disease, and sclerosteosis. Studying the mechanism of Wnt signaling and its interactions with other signaling pathways in bone will provide potential therapeutic targets to treat these bone diseases.

Multifarious effects of 17-β-estradiol on apolipoprotein E receptors gene expression during osteoblast differentiation <i>in vitro </i>

“…About twenty years ago, causal mutations in the LRP5 gene were identified to be involved in two rare bone disorders, which were related to the Wnt/β-catenin pathway (54)(55)(56). A number of reports were exploded to highlight the role of the Wnt/β-catenin pathway in the regulation of bone homeostasis (57)(58)(59). Recently, the most highlighted members of the LDLR family involved in the maintenance of bone metabolism were LRP5, LRP6, LRP4, and Apoer2 (26,60).…”

A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs

“…Bone dysfunction is associated with diverse conditions, such as osteoporosis, fracture and rheumatoid arthritis 1. Bone is also highly dynamic and is constantly remodelled by an orchestrated balance between osteoclastic bone resorption and osteoblastic bone formation 3. However, an increase in marrow adipose tissue content and decreased bone volume have also been observed in osteoporosis, diabetes and ovariectomy because of an imbalance between adipogenesis and osteogenesis from mesenchymal stem cells (MSCs) 4.…”

“…However, an increase in marrow adipose tissue content and decreased bone volume have also been observed in osteoporosis, diabetes and ovariectomy because of an imbalance between adipogenesis and osteogenesis from mesenchymal stem cells (MSCs) 4. Furthermore, there is evidence that this unbalanced proadipocytic and anti‐osteoblastic MSCs allocation could result from inhibition of the TGF‐β/BMP and Wnt/β‐catenin signalling pathways 3, 5…”

Glucocorticoid inhibits cell proliferation in differentiating osteoblasts by microRNA-199a targeting of WNT signaling

“…Therefore, further studies need to be performed to uncover the role of GC-regulated miR-199a-5p in osteoblasts. WNT/b-catenin signaling plays an important role in bone development and metabolism by controlling both bone formation and resorption (Wang et al 2014). Wnt ligands are secreted molecules that bind to cell-surface receptors that are encoded by the Frizzled and LDL-receptor-related proteins.…”