Related Experiment Video

Updated: Mar 9, 2026

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines
06:00

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines

Published on: September 13, 2017

7.6K

Celecoxib inhibits osteoblast maturation by suppressing the expression of Wnt target genes

Akihiro Nagano1, Masaki Arioka2, Fumi Takahashi-Yanaga3

  • 1Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan; Periodontology Section, Division of Oral Rehabilitation, Faculty of Dental Sciences, Kyushu University, Fukuoka, Japan.

Journal of Pharmacological Sciences
|December 24, 2016
PubMed

Insights

Celecoxib, a non-steroidal anti-inflammatory drug (NSAID), inhibits osteoblast maturation by suppressing Wnt pathway target genes, potentially explaining how NSAIDs impair bone healing and fracture repair.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Orthopedics

Background:

  • Non-steroidal anti-inflammatory drugs (NSAIDs) are known to impede bone healing.
  • Celecoxib, a COX-2 selective NSAID, was previously shown to inhibit the Wnt/β-catenin pathway in colon cancer cells.
  • The Wnt/β-catenin pathway is crucial for osteoblast development and differentiation.

Purpose of the Study:

  • To investigate the impact of celecoxib on the maturation of osteoblast-like MC3T3-E1 cells.
  • To determine if celecoxib affects key Wnt pathway components and osteoblast differentiation markers.

Main Methods:

  • Treatment of MC3T3-E1 cells with celecoxib.
  • Analysis of transcription factor 7-like 2 (TCF7L2) degradation.
  • Assessment of runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP) expression and promoter activity.
  • Evaluation of osteoblast-mediated mineralization.

Main Results:

  • Celecoxib induced degradation of TCF7L2, a critical Wnt pathway transcription factor.
  • Celecoxib suppressed the expression of RUNX2 and ALP, key osteoblast differentiation markers, by inhibiting their promoter activity.
  • Significant inhibition of osteoblast-mediated mineralization was observed in celecoxib-treated cells.

Conclusions:

  • Celecoxib inhibits osteoblast maturation through the suppression of Wnt pathway target genes.
  • This mechanism may underlie the detrimental effects of NSAIDs on bone formation and fracture healing.
Keywords:
CelecoxibFracture healingMineralizationOsteoblastWnt/β-catenin signaling pathway

More Related Videos

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro07:03

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro

Published on: June 16, 2022

7.6K

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.8K
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
4.5K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.8K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.5K
Bone Formation by Endochondral Ossification01:24

Bone Formation by Endochondral Ossification

Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
10.7K