1. Hypoxia Activates the PTHrP –MEF2C Pathway to Attenuate Hypertrophy in Mesenchymal Stem Cell Derived Cartilage
- Author
-
Stephen J. Elliman, David C. Browe, Frank Barry, Cynthia M. Coleman, Science Foundation Ireland, and Seventh Framework Programme
- Subjects
Cartilage, Articular ,0301 basic medicine ,PROMOTES ,lcsh:Medicine ,HORMONE-RELATED PROTEIN ,Mice ,0302 clinical medicine ,MEF2C ,Anaerobiosis ,lcsh:Science ,IN-VITRO CHONDROGENESIS ,Multidisciplinary ,MEF2 Transcription Factors ,Chemistry ,Hyaline cartilage ,Cell Hypoxia ,Cell biology ,DIFFERENTIATION ,medicine.anatomical_structure ,ATDC5 ,030220 oncology & carcinogenesis ,Chondrogenesis ,EXPRESSION ,medicine.medical_specialty ,Glycine ,LINE ,Mesenchymal Stem Cell Transplantation ,Article ,03 medical and health sciences ,Chondrocytes ,In vivo ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,TRANSPLANTATION ,Cartilage ,lcsh:R ,Mesenchymal stem cell ,Parathyroid Hormone-Related Protein ,Mesenchymal Stem Cells ,Prolyl-Hydroxylase Inhibitors ,Hypertrophy ,Isoquinolines ,CALCIFICATION ,Transplantation ,030104 developmental biology ,Endocrinology ,Cell culture ,lcsh:Q - Abstract
Articular cartilage lacks an intrinsic repair capacity and due to the ability of mesenchymal stem cells (MSCs) to differentiate into chondrocytes, MSCs have been touted as a cellular source to regenerate damaged cartilage. However, a number of prevailing concerns for such a treatment remain. Generally, administration of MSCs into a cartilage defect results in poor regeneration of the damaged cartilage with the repaired cartilage consisting primarily of fibro-cartilage rather than hyaline cartilage. Methods that improve the chondrogenic potential of transplanted MSCs in vivo may be advantageous. In addition, the proclivity of MSC-derived cartilage to undergo hypertrophic differentiation or form bone in vivo also remains a clinical concern. If MSC-derived cartilage was to undergo hypertrophic differentiation in vivo, this would be deleterious in a clinical setting. This study focuses on establishing a mechanism of action by which hypoxia or low oxygen tension can be used to both enhance chondrogenesis and attenuate hypertrophic differentiation of both MSC and ATDC5 derived chondrocytes. Having elucidated a novel mechanism of action, the subsequent goals of this study were to develop an in vitro culture regime to mimic the beneficial effects of physiological low oxygen tension in a normoxic environment.
- Published
- 2019