Chrystalleni Hadjicharalambous1,2, Vasileia Ismini Alexaki3, Kalliopi Alpantaki4, Maria Chatzinikolaidou5,6. 1. Department of Materials Science and Technology, University of Crete, Heraklio, Greece. 2. Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH), Heraklion, Greece. 3. Department of Clinical Pathobiochemistry, Medical Faculty, Technische Universität Dresden, Dresden, Germany. Ismini.Alexaki@uniklinikum-dresden.de. 4. Department of Orthopedics and Trauma, University Hospital of Heraklion, Crete, Greece. 5. Department of Materials Science and Technology, University of Crete, Heraklio, Greece. mchatzin@materials.uoc.gr. 6. Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH), Heraklion, Greece. mchatzin@materials.uoc.gr.
Abstract
OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs), used in the treatment of musculoskeletal pathologies, have been associated with impaired bone healing, possibly through inhibition of osteogenic differentiation. The adipose tissue (AT) is regarded as an attractive source of stromal cells for autologous cell transplantation in the bone. The effects of NSAIDs on human AT-derived stromal cells (hADSCs) are unknown. METHODS: We examined the effect of several NSAIDs including meloxicam, parecoxib, lornoxicam, diclofenac and paracetamol on the proliferation of hADSCs by means of the PrestoBlue® viability assay, and the osteogenic differentiation capacity of hADSCs by means of the alkaline phosphatase (ALP) activity, calcium deposition by alizarin red staining and osteogenic gene expression by semi-quantitative PCR. KEY FINDINGS: Most of the drugs enhanced hADSC cell growth, while either positively affecting or not influencing alkaline phosphatase (ALP) activity, calcium deposition and osteogenic gene expression. Moreover, selective COX-2 inhibitor NSAIDs, such as meloxicam or parecoxib, were advantageous over the non-selective COX-1 and COX-2 inhibitor NSAIDs lornoxicam and diclofenac. CONCLUSIONS: Altogether through this study, we show that NSAIDs, possibly depending on their selectivity for COX inhibition, leave the osteogenic differentiation capacity of hADSCs unaltered or might even enhance it.
OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs), used in the treatment of musculoskeletal pathologies, have been associated with impaired bone healing, possibly through inhibition of osteogenic differentiation. The adipose tissue (AT) is regarded as an attractive source of stromal cells for autologous cell transplantation in the bone. The effects of NSAIDs on human AT-derived stromal cells (hADSCs) are unknown. METHODS: We examined the effect of several NSAIDs including meloxicam, parecoxib, lornoxicam, diclofenac and paracetamol on the proliferation of hADSCs by means of the PrestoBlue® viability assay, and the osteogenic differentiation capacity of hADSCs by means of the alkaline phosphatase (ALP) activity, calcium deposition by alizarin red staining and osteogenic gene expression by semi-quantitative PCR. KEY FINDINGS: Most of the drugs enhanced hADSC cell growth, while either positively affecting or not influencing alkaline phosphatase (ALP) activity, calcium deposition and osteogenic gene expression. Moreover, selective COX-2 inhibitor NSAIDs, such as meloxicam or parecoxib, were advantageous over the non-selective COX-1 and COX-2 inhibitor NSAIDs lornoxicam and diclofenac. CONCLUSIONS: Altogether through this study, we show that NSAIDs, possibly depending on their selectivity for COX inhibition, leave the osteogenic differentiation capacity of hADSCs unaltered or might even enhance it.