Related Experiment Video
Updated: Jun 16, 2026
Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
The effects of COX-2 inhibitor during osteogenic differentiation of bone marrow-derived human mesenchymal stem cells
Dong Suk Yoon1, Je Hyun Yoo, Yun Hee Kim
1Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea.
Abstract:
Cyclooxygenase-2 (COX-2) inhibitors suppress bone repair and bone formation by suppressing angiogenesis as well as potentially interfering with osteoblast and osteoclast functions. In spite of these reports, there is a controversy over the exact effects of COX-2 inhibitors on bone formation processes itself. This work was designed to investigate the effect of COX-2 inhibitor on osteogenesis of human bone marrow-derived mesenchymal stem cells (MSC). MSCs in osteogenesis were treated with COX-2 inhibitor (celecoxib and naproxen) in the absence or presence of interleukin-1β (IL-1β), which was used to induce inflammation. Following differentiation, alkaline phosphatase (ALP) and calcium contents of IL-1β-treated MSC were significantly reduced by high doses of COX-2 inhibitors compared with the low-dose group. However, in non-inflammatory-conditioned MSCs, ALP and calcium contents were not reduced by COX-2 inhibitors. The mRNA expression of Runx2/Cbf alpha 1, Dlx5, and osteocalcin was also decreased by COX-2 inhibitors in inflammatory-conditioned MSCs and showed a significant decrease for the high dose while they remained constant in the non-inflammatory-conditioned MSCs. These data indicate that the osteogenic potential of MSC is inhibited/delayed by the treatment of high-dose NSAIDs under inflammatory conditions.
Insights
High-dose NSAIDs, specifically cyclooxygenase-2 (COX-2) inhibitors, impair bone formation in human mesenchymal stem cells (MSCs) during inflammation. These COX-2 inhibitors did not affect MSCs in non-inflammatory conditions.
Area of Science:
- Biomedical Science
- Cell Biology
- Orthopedics
Background:
- Cyclooxygenase-2 (COX-2) inhibitors' effects on bone formation are debated.
- COX-2 inhibitors may impact osteoblast and osteoclast functions and angiogenesis, potentially hindering bone repair.
Purpose of the Study:
- To investigate the impact of COX-2 inhibitors on the osteogenesis of human bone marrow-derived mesenchymal stem cells (MSCs).
- To determine if inflammation influences the effect of COX-2 inhibitors on MSC osteogenesis.
Main Methods:
- Human bone marrow-derived MSCs were cultured and induced to differentiate into osteoblasts.
- Cells were treated with COX-2 inhibitors (celecoxib, naproxen) with or without interleukin-1β (IL-1β) to simulate inflammation.
- Alkaline phosphatase (ALP) activity, calcium content, and gene expression (Runx2, Dlx5, osteocalcin) were analyzed.
Main Results:
- High doses of COX-2 inhibitors significantly reduced ALP and calcium content in IL-1β-treated MSCs.
- In non-inflammatory conditions, COX-2 inhibitors did not affect ALP and calcium levels.
- mRNA expression of key osteogenic genes was downregulated by high-dose COX-2 inhibitors in inflammatory conditions but not in non-inflammatory conditions.
Conclusions:
- High-dose NSAIDs (COX-2 inhibitors) inhibit or delay MSC osteogenic potential under inflammatory conditions.
- The anti-osteogenic effect of COX-2 inhibitors is dependent on the presence of inflammation.
