Wnt16
Wnt16 encodes a secreted Wnt ligand, and Wnt ligands bind cell-surface receptors to activate canonical or non-canonical Wnt signaling pathways that regulate development, adult tissue homeostasis, and disease mechanisms[1]. In bone research, WNT16 is a physiological regulator of bone mass and fracture susceptibility, and glucocorticoid treatment decreases Wnt16 mRNA in bone while osteoblast-lineage WNT16 overexpression partly protects mice from glucocorticoid-induced bone loss[2]. Mechanistically, inflammatory oncostatin M robustly increases Wnt16 mRNA in mouse calvarial osteoblasts through gp130, OSMR, and SHC1/STAT3 signaling, and WNT16 limits oncostatin M-induced osteoclast formation as a negative feedback regulator[3]. Compared with related Wnt isoforms, WNT16A and WNT16B arise from alternative 5′ regions and first exons, with WNT16A expressed mainly in adult pancreas and WNT16B showing broader adult tissue expression[4]. In disease models, WNT16B marks cellular senescence, supports p53-dependent p21 activation, and regulates PI3K/AKT signaling[5]. For experimental applications, WNT16B promotes human limbal epithelial stem/progenitor cell proliferation and self-renewal through a non-canonical calcium/calcineurin A/NFATC2 pathway, supporting corneal epithelial repair models[6].
References:
- [1]. Hu L, et al. Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease. Bone Res. 2024 Jul 10;12(1):39. [Content Brief]
- [2]. Ohlsson C, et al. WNT16 overexpression partly protects against glucocorticoid-induced bone loss. Am J Physiol Endocrinol Metab. 2018 Jun 1;314(6):E597-E604. [Content Brief]
- [3]. Henning P, et al. WNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M. J Inflamm Res. 2021 Sep 18;14:4723-4741. [Content Brief]
- [4]. Fear MW, et al. Wnt-16a, a novel Wnt-16 isoform, which shows differential expression in adult human tissues. Biochem Biophys Res Commun. 2000 Nov 30;278(3):814-20. [Content Brief]
- [5]. Binet R, et al. WNT16B is a new marker of cellular senescence that regulates p53 activity and the phosphoinositide 3-kinase/AKT pathway. Cancer Res. 2009 Dec 15;69(24):9183-91. [Content Brief]
- [6]. Wan X, et al. WNT16b promotes the proliferation and self-renewal of human limbal epithelial stem/progenitor cells via activating the calcium/calcineurin A/NFATC2 pathway. Cell Prolif. 2023 Oct;56(10):e13460. [Content Brief]
