Endogenous Articular Cartilage Regeneration After Injury
| dc.contributor.advisor | Krawetz, Roman J. | |
| dc.contributor.author | Jablonski, Christina Lynn | |
| dc.contributor.committeemember | Cobb, John A. | |
| dc.contributor.committeemember | McCafferty, Donna Marie | |
| dc.contributor.committeemember | Salo, Paul T. | |
| dc.contributor.committeemember | Manske, Sarah Lynn | |
| dc.date | 2019-06 | |
| dc.date.accessioned | 2019-01-29T21:36:46Z | |
| dc.date.available | 2019-01-29T21:36:46Z | |
| dc.date.issued | 2019-01-21 | |
| dc.description.abstract | Once injured, articular cartilage cannot regenerate, and a consequence of this inadequacy is osteoarthritis (OA), a chronic, degenerative joint disorder. Mesenchymal stem cells (MSCs) have shown promise in the treatment of cartilage injuries as they possess immunomodulatory properties and can differentiate into chondrocytes (e.g. cartilage cells). However, the outcomes of MSC-based therapies to date have been highly-variable, illustrating our incomplete understanding of how MSCs function in the joint. Superior cartilage healing post-injury has been observed in the MRL ‘super-healer’ mouse and has been linked to a deficiency in the cell cycle regulator, p21. Therefore, the purpose of this thesis was to determine the cell type(s) and/or mechanism(s) involved in endogenous cartilage regeneration in p21-/- mice. To accomplish this, we lineage traced Prx1+ (transcription factor specific to mesenchymal cells) MSC/progenitors in vivo after cartilage injury in p21-/- and C57 wild-type mice. We further examined the inflammatory cytokine profile of mice in the presence/absence of p21 and functionally tested the role of the CCL2/CCR2 signalling axis, which was found to be altered in p21-/- mice in response to cartilage injury. While deletion of p21 resulted in endogenous articular cartilage regeneration, Prx1+ MSC/progenitors did not differentiate into the new cartilage and/or subchondral bone observed in p21-/- mice. Furthermore, few differences in cell number (e.g. MSCs/stem cells, macrophages, proliferating cells) were observed between p21-/- mice and C57 wild-type mice suggesting that secreted factors or additional cell types may be responsible for the cartilage regeneration observed. To support this hypothesis, we further demonstrated that the cartilage regeneration ability of p21-/- mice could be recapitulated through deletion of the chemokine receptor CCR2, yet if its ligand CCL2 was deleted, cartilage regeneration ability was lost. Future studies using additional lineage reporter mice in the context of p21 deletion will be necessary to determine the cell(s)/factor(s) responsible for cartilage regeneration in these mice and to determine if targeting the cell cycle has potential as a safe and effective therapeutic strategy for treating cartilage injuries and/or OA. | en_US |
| dc.identifier.citation | Jablonski, C. L. (2019). Endogenous articular cartilage regeneration after injury (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/36126 | |
| dc.identifier.uri | http://hdl.handle.net/1880/109869 | |
| dc.language.iso | en | en_US |
| dc.publisher.faculty | Arts | en_US |
| dc.publisher.institution | University of Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | en_US |
| dc.subject | Osteoarthritis | en_US |
| dc.subject | p21 | en_US |
| dc.subject | Prx1 | en_US |
| dc.subject | mesenchymal stem cells | en_US |
| dc.subject | articular cartilage | en_US |
| dc.subject | cartilage regeneration | en_US |
| dc.subject.classification | Engineering--Biomedical | en_US |
| dc.title | Endogenous Articular Cartilage Regeneration After Injury | en_US |
| dc.type | doctoral thesis | en_US |
| thesis.degree.discipline | Engineering – Biomedical | en_US |
| thesis.degree.grantor | University of Calgary | en_US |
| thesis.degree.name | Doctor of Philosophy (PhD) | en_US |
| ucalgary.item.requestcopy | true |