2019 Volume No 38 – pages 106-122
Title: Collagen type X is essential for successful mesenchymal stem cell-mediated cartilage formation and subsequent endochondral ossification |
Authors: CA Knuth, E Andres Sastre, NB Fahy, J Witte-Bouma, Y Ridwan, EM Strabbing, MJ Koudstaal, J van de Peppel, EB Wolvius, R Narcisi, E Farrell |
Address: Department of Oral and Maxillofacial Surgery, Special Dental Care and Orthodontics, Erasmus MC, 3000 DR Rotterdam, the Netherlands |
E-mail: e.farrell at erasmusmc.nl |
Abstract: In tissue engineering, endochondral ossification (EO) is often replicated by chondrogenically differentiating mesenchymal stromal cells (MSCs) in vitro and achieving bone formation through in vivo implantation. The resulting marrow-containing bone constructs are promising as a treatment for bone defects. However, limited bone formation capacity has prevented them from reaching their full potential. This is further complicated since it is not fully understood how this bone formation is achieved. Acellular grafts derived from chondrogenically differentiated MSCs can initiate bone formation; however, which component within these decellularised matrices contribute to bone formation has yet to be determined. Collagen type X (COLX), a hypertrophy-associated collagen found within these constructs, is involved in matrix organisation, calcium binding and matrix vesicle compartmentalisation. However, the importance of COLX during tissue-engineered chondrogenesis and subsequent bone formation is unknown. The present study investigated the importance of COLX by shRNA-mediated gene silencing in primary MSCs. A significant knock-down of COLX disrupted the production of extracellular matrix key components and the secretion profile of chondrogenically differentiated MSCs. Following in vivo implantation, disrupted bone formation in knock-down constructs was observed. The importance of COLX was confirmed during both chondrogenic differentiation and subsequent EO in this tissue engineered setting. |
Key Words: Collagen type X, endochondral ossification, regenerative medicine, bone tissue engineering, mesenchymal stem cells, chondrogenesis. |
Publication date: September 18th 2019 |
Article download: Pages
106-122 (PDF file) |
