Exploring a Nitric Oxide-Releasing Celecoxib Derivative as a Potential Modulator of Bone Healing: Insights from Ex Vivo and In Vivo Imaging Experiments

Neuber, Christin; Niedenzu, Luisa; Schulze, Sabine; Laube, Markus; Hofheinz, Frank; Rammelt, Stefan; Pietzsch, Jens

doi:10.3390/ijms26062582

Open AccessArticle

Exploring a Nitric Oxide-Releasing Celecoxib Derivative as a Potential Modulator of Bone Healing: Insights from Ex Vivo and In Vivo Imaging Experiments

by

Christin Neuber

^1,*

,

Luisa Niedenzu

²,

Sabine Schulze

²

,

Markus Laube

¹

,

Frank Hofheinz

³,

Stefan Rammelt

²

and

Jens Pietzsch

^1,4

¹

Department Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany

²

University Center for Orthopaedics, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany

³

Department Positron Emission Tomography, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany

⁴

Faculty of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(6), 2582; https://doi.org/10.3390/ijms26062582

Submission received: 27 January 2025 / Revised: 21 February 2025 / Accepted: 6 March 2025 / Published: 13 March 2025

(This article belongs to the Special Issue Advances in Bone Growth, Development and Metabolism)

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Abstract

The inducible enzyme cyclooxygenase-2 (COX-2) and the subsequent synthesis of eicosanoids initiated by this enzyme are important molecular players in bone healing. In this pilot study, the suitability of a novel selective COX-2 inhibitor bearing a nitric oxide (NO)-releasing moiety was investigated as a modulator of healing a critical-size bone defect in rats. A 5 mm femoral defect was randomly filled with no material (negative control, NC), a mixture of collagen and autologous bone fragments (positive control, PC), or polycaprolactone-co-lactide (PCL)-scaffolds coated with two types of artificial extracellular matrix (aECM; collagen/chondroitin sulfate (Col/CS) or collagen/polysulfated hyaluronic acid (Col/sHA3)). Bone healing was monitored by a dual-tracer ([¹⁸F]FDG/[¹⁸F]fluoride) approach using PET/CT imaging in vivo. In addition, ex vivo µCT imaging as well as histological and immunohistochemical studies were performed 16 weeks post-surgery. A significant higher uptake of [¹⁸F]FDG, a surrogate marker for inflammatory infiltrate, but not of [¹⁸F]fluoride, representing bone mineralization, was observed in the implanted PCL-scaffolds coated with either Col/CS or Col/sHA3. Molecular targeting of COX-2 with NO-coxib had no significant effect on tracer uptake in any of the groups. Histological and immunohistochemical staining showed no evidence of a positive or negative influence of NO-coxib treatment on bone healing.

Keywords: bone healing; inflammation; cyclooxygenase-2; revascularization; molecular imaging; small animal imaging; positron emission tomography; dual-radiotracer approach; rat critical bone defect

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MDPI and ACS Style

Neuber, C.; Niedenzu, L.; Schulze, S.; Laube, M.; Hofheinz, F.; Rammelt, S.; Pietzsch, J. Exploring a Nitric Oxide-Releasing Celecoxib Derivative as a Potential Modulator of Bone Healing: Insights from Ex Vivo and In Vivo Imaging Experiments. Int. J. Mol. Sci. 2025, 26, 2582. https://doi.org/10.3390/ijms26062582

AMA Style

Neuber C, Niedenzu L, Schulze S, Laube M, Hofheinz F, Rammelt S, Pietzsch J. Exploring a Nitric Oxide-Releasing Celecoxib Derivative as a Potential Modulator of Bone Healing: Insights from Ex Vivo and In Vivo Imaging Experiments. International Journal of Molecular Sciences. 2025; 26(6):2582. https://doi.org/10.3390/ijms26062582

Chicago/Turabian Style

Neuber, Christin, Luisa Niedenzu, Sabine Schulze, Markus Laube, Frank Hofheinz, Stefan Rammelt, and Jens Pietzsch. 2025. "Exploring a Nitric Oxide-Releasing Celecoxib Derivative as a Potential Modulator of Bone Healing: Insights from Ex Vivo and In Vivo Imaging Experiments" International Journal of Molecular Sciences 26, no. 6: 2582. https://doi.org/10.3390/ijms26062582

APA Style

Neuber, C., Niedenzu, L., Schulze, S., Laube, M., Hofheinz, F., Rammelt, S., & Pietzsch, J. (2025). Exploring a Nitric Oxide-Releasing Celecoxib Derivative as a Potential Modulator of Bone Healing: Insights from Ex Vivo and In Vivo Imaging Experiments. International Journal of Molecular Sciences, 26(6), 2582. https://doi.org/10.3390/ijms26062582

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Exploring a Nitric Oxide-Releasing Celecoxib Derivative as a Potential Modulator of Bone Healing: Insights from Ex Vivo and In Vivo Imaging Experiments

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