Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo.
To examine the differential mechanobiological responses of specific resident tendon cells, we developed an in vivo model of whole-body irradiation followed by injection of either tendon stem/progenitor cells (TSCs) expressing green fluorescent protein (GFP-TSCs) or mature tenocytes expressing GFP (G...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0242640 |
| _version_ | 1818681372875685888 |
|---|---|
| author | Jianying Zhang Daibang Nie Kelly Williamson Arthur McDowell MaCalus V Hogan James H-C Wang |
| author_facet | Jianying Zhang Daibang Nie Kelly Williamson Arthur McDowell MaCalus V Hogan James H-C Wang |
| author_sort | Jianying Zhang |
| collection | DOAJ |
| description | To examine the differential mechanobiological responses of specific resident tendon cells, we developed an in vivo model of whole-body irradiation followed by injection of either tendon stem/progenitor cells (TSCs) expressing green fluorescent protein (GFP-TSCs) or mature tenocytes expressing GFP (GFP-TNCs) into the patellar tendons of wild type C57 mice. Injected mice were subjected to short term (3 weeks) treadmill running, specifically moderate treadmill running (MTR) and intensive treadmill running (ITR). In MTR mice, both GFP-TSC and GFP-TNC injected tendons maintained normal cell morphology with elevated expression of tendon related markers collagen I and tenomodulin. In ITR mice injected with GFP-TNCs, cells also maintained an elongated shape similar to the shape found in normal/untreated control mice, as well as elevated expression of tendon related markers. However, ITR mice injected with GFP-TSCs showed abnormal changes, such as cell morphology transitioning to a round shape, elevated chondrogenic differentiation, and increased gene expression of non-tenocyte related genes LPL, Runx-2, and SOX-9. Increased gene expression data was supported by immunostaining showing elevated expression of SOX-9, Runx-2, and PPARγ. This study provides evidence that while MTR maintains tendon homeostasis by promoting the differentiation of TSCs into TNCs, ITR causes the onset of tendinopathy development by inducing non-tenocyte differentiation of TSCs, which may eventually lead to the formation of non-tendinous tissues in tendon tissue after long term mechanical overloading conditions on the tendon. |
| first_indexed | 2024-12-17T10:01:55Z |
| format | Article |
| id | doaj.art-f027a7688b9e4f62a33f2640a7575faf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T10:01:55Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f027a7688b9e4f62a33f2640a7575faf2022-12-21T21:53:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-011512e024264010.1371/journal.pone.0242640Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo.Jianying ZhangDaibang NieKelly WilliamsonArthur McDowellMaCalus V HoganJames H-C WangTo examine the differential mechanobiological responses of specific resident tendon cells, we developed an in vivo model of whole-body irradiation followed by injection of either tendon stem/progenitor cells (TSCs) expressing green fluorescent protein (GFP-TSCs) or mature tenocytes expressing GFP (GFP-TNCs) into the patellar tendons of wild type C57 mice. Injected mice were subjected to short term (3 weeks) treadmill running, specifically moderate treadmill running (MTR) and intensive treadmill running (ITR). In MTR mice, both GFP-TSC and GFP-TNC injected tendons maintained normal cell morphology with elevated expression of tendon related markers collagen I and tenomodulin. In ITR mice injected with GFP-TNCs, cells also maintained an elongated shape similar to the shape found in normal/untreated control mice, as well as elevated expression of tendon related markers. However, ITR mice injected with GFP-TSCs showed abnormal changes, such as cell morphology transitioning to a round shape, elevated chondrogenic differentiation, and increased gene expression of non-tenocyte related genes LPL, Runx-2, and SOX-9. Increased gene expression data was supported by immunostaining showing elevated expression of SOX-9, Runx-2, and PPARγ. This study provides evidence that while MTR maintains tendon homeostasis by promoting the differentiation of TSCs into TNCs, ITR causes the onset of tendinopathy development by inducing non-tenocyte differentiation of TSCs, which may eventually lead to the formation of non-tendinous tissues in tendon tissue after long term mechanical overloading conditions on the tendon.https://doi.org/10.1371/journal.pone.0242640 |
| spellingShingle | Jianying Zhang Daibang Nie Kelly Williamson Arthur McDowell MaCalus V Hogan James H-C Wang Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo. PLoS ONE |
| title | Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo. |
| title_full | Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo. |
| title_fullStr | Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo. |
| title_full_unstemmed | Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo. |
| title_short | Moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem/progenitor cells in vivo. |
| title_sort | moderate and intensive mechanical loading differentially modulate the phenotype of tendon stem progenitor cells in vivo |
| url | https://doi.org/10.1371/journal.pone.0242640 |
| work_keys_str_mv | AT jianyingzhang moderateandintensivemechanicalloadingdifferentiallymodulatethephenotypeoftendonstemprogenitorcellsinvivo AT daibangnie moderateandintensivemechanicalloadingdifferentiallymodulatethephenotypeoftendonstemprogenitorcellsinvivo AT kellywilliamson moderateandintensivemechanicalloadingdifferentiallymodulatethephenotypeoftendonstemprogenitorcellsinvivo AT arthurmcdowell moderateandintensivemechanicalloadingdifferentiallymodulatethephenotypeoftendonstemprogenitorcellsinvivo AT macalusvhogan moderateandintensivemechanicalloadingdifferentiallymodulatethephenotypeoftendonstemprogenitorcellsinvivo AT jameshcwang moderateandintensivemechanicalloadingdifferentiallymodulatethephenotypeoftendonstemprogenitorcellsinvivo |