NOTUM

Last update 08 May 2025

Basic Info

Synonyms

hNOTUM, NOTUM, notum, palmitoleoyl-protein carboxylesterase

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Introduction

Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway by specifically mediating depalmitoleoylation of WNT proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors (PubMed:25731175).

100 Clinical Results associated with NOTUM

100 Translational Medicine associated with NOTUM

0 Patents (Medical) associated with NOTUM

130

Literatures (Medical) associated with NOTUM

01 May 2025·Journal of Ethnopharmacology

New Qiangguyin activates Wnt/β-catenin pathway by down-regulating Notum to improve osteoporosis in rats

Article

Author: He, Xiaoming ; Xu, Yawei ; Zhang, Yingkai ; Liu, Kang ; Zhang, Xu ; Shi, Xiaolin ; Meng, Shilong ; Tang, Binbin ; Cao, Yanguang

BACKGROUNDQiangguyin (QGY) is a traditional Chinese medicine prescription for postmenopausal osteoporosis. We modified the formula based on QGY and named it new QGY (N-QGY), and studied the therapeutic mechanism of N-QGY on osteoporosis.METHODOsteoporosis rat model was established by bilateral ovariectomy, and the rats were treated with exosomes from osteoclasts treated with N-QGY. Then the bone morphological parameters were detected by micro-computed tomography, the levels of Procollagen I N-terminal Propeptide (PINP), β-crosslaps (β-CTX), Estrogen and osteocalcin (OCN) were detected by ELISA, and the expressions of Alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), Osteopontin (OPN), Notum and β-catenin were detected by Western blot. Subsequently, the primary cultured bone marrow mesenchymal stem cells (BMSCs) were transfected with Notum overexpression plasmid and co-cultured with exosomes from osteoclasts treated with N-QGY or interleukin (IL)-1β. Subsequently, the cell viability and the expression of bone formation-related genes or proteins were detected. ALP staining and alizarin red staining were performed.RESULTIn vivo, N-QGY improved the bone morphological indexes and serum levels of PINP, β-CTX, estrogen, ALP, RUNX2 and OPN in bone tissues or serum, down-regulated Notum expressions and activated β-catenin pathway in bone tissues. The exosomes derived from N-QGY-treated osteoclast alleviated the destructive effect of exosomes derived from osteoclast on osteogenic differentiation of BMSCs, which was embodied in promoting the activity of BMSCs, up-regulating the levels of ALP, RUNX2, OPN and OCN, promoting bone mineralization and activating β-catenin pathway.CONCLUSIONN-QGY activates Wnt/β-catenin pathway by down-regulating Notum to improve osteoporosis in rats.

01 Mar 2025·Advanced Biology

New‐QiangGuYin‐Containing Serum Inhibits Osteoclast‐Derived Exosome Secretion and Down‐Regulates Notum to Promote Osteoblast Differentiation

Article

Author: Yuan, Yifeng ; Yu, Yang ; Tong, Minghao ; Cao, Yanguang ; Shi, Xiaolin ; Zhang, Xu ; Liu, Kang ; Zhang, Wei ; Meng, Shilong

AbstractNew‐QiangGuYin (N‐QGY), the addition of sea buckthorn on the basis of QGY formula, is herbal formula widely used clinically in China for the treatment of osteoporosis (OP), but its mechanism warrants further exploration. The mechanisms of QGY and N‐QGY in the treatment of OP are probed from the perspective of osteoclast‐osteoblast balance. Thirty Sprague‐Dawley rats are randomly divided into N‐QGY group, QGY group, and Control group. Beyond control rats that orally took normal saline, other rats are orally administered with isometric N‐QGY or QGY twice every day for 3 days. The drug‐containing serum and control serum are prepared and their effects on osteoclast‐derived exosome secretion are determined by bicinchoninic acid assay (BCA), nanoparticle tracking analysis, and Western blot. GW4869 and Interleukin‐1β (IL‐1β) are adopted as the exosome inhibitor and inducer, respectively. Exosome uptake, cell counting kit‐8, alkaline phosphatase (ALP) staining, alizarin red staining, enzyme‐linked immunosorbent assay, quantitative real‐time polymerase chain reaction, and Western blot are performed to examine the effects of altered osteoclast exosome content on osteogenic differentiation of mesenchymal stem cells (MSCs). N‐QGY, QGY, and GW4869 inhibit osteoclast‐derived exosome secretion and exosome uptake by MSCs, whereas IL‐1β exerted the opposite effects (p < 0.05). Different from IL‐1β, N‐QGY, QGY, and GW4869 partially elevated MSC viability, osteocalcin secretion, ALP, RUNX Family Transcription Factor 2 (RUNX2) and Osteopontin (OPN) expressions, and calcium deposition in the osteoclast‐MSCs coculture system (p < 0.05). Mechanically, osteoclasts increased Notum protein level but decreased β‐catenin level, which is enhanced by IL‐1β but is reversed by GW4869, QGY, and N‐QGY (p < 0.05). And the effect of N‐QGY is more conspicuous than that of QGY (P<0.05). N‐QGY‐containing serum inhibits exosome levels in osteoclasts, thereby enhancing osteogenic differentiation of MSCs via inhibition of Notum protein and promotion of β‐catenin protein.

01 Mar 2025·Bioorganic Chemistry

Targeting Wnt signaling pathway with small-molecule therapeutics for treating osteoporosis

Review

Author: Hussain, Mohd Kamil ; Ahamad, Shakir ; Saquib, Mohammad ; Bhat, Shahnawaz Ali

Small molecules are emerging as potential candidates for treating osteoporosis by activating canonical Wnt signaling. These candidates work either by inhibiting DKK-1, sclerostin, SFRP-1, NOTUM, and S1P lyase or by preventing β-catenin degradation through inhibition of GSK-3β, or by targeting Dvl-CXXC5 and axin/β-catenin interactions. While many of these anti-osteoporotic small molecules are in preclinical development, the paucity of FDA-approved small molecules, or promising candidates, that have progressed to clinical trials for treating bone disorders through this mechanism poses a challenge. Despite advancements in computer-aided drug design, it is rarely employed for designing Wnt signaling activators to treat osteoporosis, and high-throughput screen (HTS) remains the primary method for discovering initial hits. Acknowledging the promising therapeutic potential of these compounds in addressing bone diseases, this review underscores the need for further mechanistic elucidation to enhance our understanding of their applications. Additionally, caution must be exercised in the design of small molecule-based Wnt activators due to their association with oncological risks.

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