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PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification
Heterotopic ossification (HO) is a debilitating condition defined by the rapid formation of bone in soft tissues. What makes HO fascinating is firstly the rate at which bone is deposited, and secondly the fact that this bone is structurally and compositionally similar to that of a healthy adult. If...
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| Format: | Default Article |
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2017
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| Online Access: | https://hdl.handle.net/2134/23009 |
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| _version_ | 1818167115372298240 |
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| author | Owen Davies L.M. Grover Mark Lewis Yang Liu |
| author_facet | Owen Davies L.M. Grover Mark Lewis Yang Liu |
| author_sort | Owen Davies (1253895) |
| collection | Figshare |
| description | Heterotopic ossification (HO) is a debilitating condition defined by the rapid formation of bone in soft tissues. What makes HO fascinating is firstly the rate at which bone is deposited, and secondly the fact that this bone is structurally and compositionally similar to that of a healthy adult. If the mechanisms governing HO are understood, they have the potential to be exploited for the development of potent osteoinductive therapies. With this aim, we utilised a tissue engineered skeletal muscle model to better understand the role of inflammation on this debilitating phenomenon. We showed myoblasts could be divided into two distinct populations, myogenic cells and undifferentiated "reserve" cells. Gene expression analysis of myogenic and osteo-regulatory markers confirmed that "reserve" cells were primed for osteogenic differentiation, but had a reduced capacity for myogenesis. Osteogenic differentiation was significantly enhanced in the presence of PDGF-BB and BMP2, and correlated with conversion to a Sca-1(+) /CD73(+) phenotype. Alizarin red staining showed that PDGF-BB promoted significantly more mineral deposition than BMP2. Finally, we showed that PDGF-induced mineralisation was blocked in the presence of the pro-inflammatory cytokines TNFα and IL1. In conclusion, the present study identified that PDGF-BB is a potent osteoinductive factor in a model of tissue engineered skeletal muscle, and that the osteogenic capacity of this protein was modulated in the presence of pro-inflammatory cytokines. These findings reveal a possible mechanism by which HO develops following trauma. Importantly, these findings have implications for the induction and control of bone formation for regenerative medicine. |
| format | Default Article |
| id | rr-article-9564830 |
| institution | Loughborough University |
| publishDate | 2017 |
| record_format | Figshare |
| spelling | rr-article-95648302017-03-20T00:00:00Z PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification Owen Davies (1253895) L.M. Grover (7212113) Mark Lewis (1255254) Yang Liu (1257603) Other health sciences not elsewhere classified Bone Heterotopic ossification PDGF Skeletal muscle inflammation osteoprogenitor Medical and Health Sciences not elsewhere classified Heterotopic ossification (HO) is a debilitating condition defined by the rapid formation of bone in soft tissues. What makes HO fascinating is firstly the rate at which bone is deposited, and secondly the fact that this bone is structurally and compositionally similar to that of a healthy adult. If the mechanisms governing HO are understood, they have the potential to be exploited for the development of potent osteoinductive therapies. With this aim, we utilised a tissue engineered skeletal muscle model to better understand the role of inflammation on this debilitating phenomenon. We showed myoblasts could be divided into two distinct populations, myogenic cells and undifferentiated "reserve" cells. Gene expression analysis of myogenic and osteo-regulatory markers confirmed that "reserve" cells were primed for osteogenic differentiation, but had a reduced capacity for myogenesis. Osteogenic differentiation was significantly enhanced in the presence of PDGF-BB and BMP2, and correlated with conversion to a Sca-1(+) /CD73(+) phenotype. Alizarin red staining showed that PDGF-BB promoted significantly more mineral deposition than BMP2. Finally, we showed that PDGF-induced mineralisation was blocked in the presence of the pro-inflammatory cytokines TNFα and IL1. In conclusion, the present study identified that PDGF-BB is a potent osteoinductive factor in a model of tissue engineered skeletal muscle, and that the osteogenic capacity of this protein was modulated in the presence of pro-inflammatory cytokines. These findings reveal a possible mechanism by which HO develops following trauma. Importantly, these findings have implications for the induction and control of bone formation for regenerative medicine. 2017-03-20T00:00:00Z Text Journal contribution 2134/23009 https://figshare.com/articles/journal_contribution/PDGF_is_a_potent_initiator_of_bone_formation_in_a_tissue_engineered_model_of_pathological_ossification/9564830 CC BY 4.0 |
| spellingShingle | Other health sciences not elsewhere classified Bone Heterotopic ossification PDGF Skeletal muscle inflammation osteoprogenitor Medical and Health Sciences not elsewhere classified Owen Davies L.M. Grover Mark Lewis Yang Liu PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification |
| title | PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification |
| title_full | PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification |
| title_fullStr | PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification |
| title_full_unstemmed | PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification |
| title_short | PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification |
| title_sort | pdgf is a potent initiator of bone formation in a tissue engineered model of pathological ossification |
| topic | Other health sciences not elsewhere classified Bone Heterotopic ossification PDGF Skeletal muscle inflammation osteoprogenitor Medical and Health Sciences not elsewhere classified |
| url | https://hdl.handle.net/2134/23009 |