Int. J. Mol. Sci. 2017, 18(12), 2517; https://doi.org/10.3390/ijms18122517
Ascorbic Acid Attenuates Senescence of Human Osteoarthritic Osteoblasts
Maximilian G. Burger 1,2,†, Amir Steinitz 1,3,†
, Jeroen Geurts 4, Benjamin E. Pippenger 4, Dirk J. Schaefer 2, Ivan Martin 1, Andrea Barbero 1,*
and Karoliina Pelttari 1
, Jeroen Geurts 4, Benjamin E. Pippenger 4, Dirk J. Schaefer 2, Ivan Martin 1, Andrea Barbero 1,*
and Karoliina Pelttari 11
Department of Biomedicine, University of Basel, University Hospital of Basel, 4031 Basel, Switzerland
2
Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, University of Basel, 4031 Basel, Switzerland
3
Departments for Orthopedic Surgery and Traumatology, University Hospital of Basel, 4031 Basel, Switzerland
4
Departments Spine Surgery and Biomedical Engineering, University Hospital of Basel, University of Basel, 4031 Basel, Switzerland
†
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 4 October 2017 / Revised: 8 November 2017 / Accepted: 20 November 2017 / Published: 24 November 2017
(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)
Abstract
The accumulation of senescent cells is implicated in the pathology of several age-related diseases. While the clearance of senescent cells has been suggested as a therapeutic target for patients with osteoarthritis (OA), cellular senescence of bone-resident osteoblasts (OB) remains poorly explored. Since oxidative stress is a well-known inducer of cellular senescence, we here investigated the effect of antioxidant supplementation on the isolation efficiency, expansion, differentiation potential, and transcriptomic profile of OB from osteoarthritic subchondral bone. Bone chips were harvested from sclerotic and non-sclerotic regions of the subchondral bone of human OA joints. The application of 0.1 mM ascorbic acid-2-phosphate (AA) significantly increased the number of outgrowing cells and their proliferation capacity. This enhanced proliferative capacity showed a negative correlation with the amount of senescent cells and was accompanied by decreased expression of reactive oxygen species (ROS) in cultured OB. Expanded cells continued to express differentiated OB markers independently of AA supplementation and demonstrated no changes in their capacity to osteogenically differentiate. Transcriptomic analyses revealed that apoptotic, cell cycle–proliferation, and catabolic pathways were the main pathways affected in the presence of AA during OB expansion. Supplementation with AA can thus help to expand subchondral bone OB in vitro while maintaining their special cellular characteristics. The clearance of such senescent OB could be envisioned as a potential therapeutic target for the treatment of OA. View Full-TextKeywords:
osteoblast; osteoarthritis; oxidative stress; senescence; subchondral bone; transcriptomics
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Burger, M.G.; Steinitz, A.; Geurts, J.; Pippenger, B.E.; Schaefer, D.J.; Martin, I.; Barbero, A.; Pelttari, K. Ascorbic Acid Attenuates Senescence of Human Osteoarthritic Osteoblasts. Int. J. Mol. Sci. 2017, 18, 2517.
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