Aggrecan and COMP Improve Periosteal Chondrogenesis by Delaying Chondrocyte Hypertrophic Maturation
The generation of cartilage from progenitor cells for the purpose of cartilage repair is often hampered by hypertrophic differentiation of the engineered cartilaginous tissue caused by endochondral ossification. Since a healthy cartilage matrix contains high amounts of Aggrecan and COMP, we hypothes...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2020.01036/full |
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| author | Marjolein M. J. Caron Maarten P. F. Janssen Laura Peeters Dominik R. Haudenschild Andy Cremers Don A. M. Surtel Lodewijk W. van Rhijn Pieter J. Emans Tim J. M. Welting |
| author_facet | Marjolein M. J. Caron Maarten P. F. Janssen Laura Peeters Dominik R. Haudenschild Andy Cremers Don A. M. Surtel Lodewijk W. van Rhijn Pieter J. Emans Tim J. M. Welting |
| author_sort | Marjolein M. J. Caron |
| collection | DOAJ |
| description | The generation of cartilage from progenitor cells for the purpose of cartilage repair is often hampered by hypertrophic differentiation of the engineered cartilaginous tissue caused by endochondral ossification. Since a healthy cartilage matrix contains high amounts of Aggrecan and COMP, we hypothesized that their supplementation in the biogel used in the generation of subperiosteal cartilage mimics the composition of the cartilage extracellular matrix environment, with beneficial properties for the engineered cartilage. Supplementation of COMP or Aggrecan was studied in vitro during chondrogenic differentiation of rabbit periosteum cells and periosteum-derived chondrocytes. Low melting agarose was supplemented with bovine Aggrecan, human recombinant COMP or vehicle and was injected between the bone and periosteum at the upper medial side of the tibia of New Zealand white rabbits. Generated subperiosteal cartilage tissue was analyzed for weight, GAG and DNA content and ALP activity. Key markers of different phases of endochondral ossification were measured by RT-qPCR. For the in vitro experiments, no significant differences in chondrogenic marker expression were detected following COMP or Aggrecan supplementation, while in vivo favorable chondrogenic marker expression was detected. Gene expression levels of hypertrophic markers as well as ALP activity were significantly decreased in the Aggrecan and COMP supplemented conditions compared to controls. The wet weight and GAG content of the in vivo generated subperiosteal cartilage tissue was not significantly different between groups. Data demonstrate the potential of Aggrecan and COMP to favorably influence the subperiosteal microenvironment for the in vivo generation of cartilage for the optimization of cartilage regenerative approaches. |
| first_indexed | 2024-12-14T23:27:49Z |
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| id | doaj.art-36dffda142384c068a95fe5f22f5ffe5 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-14T23:27:49Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-36dffda142384c068a95fe5f22f5ffe52022-12-21T22:43:46ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-08-01810.3389/fbioe.2020.01036551031Aggrecan and COMP Improve Periosteal Chondrogenesis by Delaying Chondrocyte Hypertrophic MaturationMarjolein M. J. Caron0Maarten P. F. Janssen1Laura Peeters2Dominik R. Haudenschild3Andy Cremers4Don A. M. Surtel5Lodewijk W. van Rhijn6Pieter J. Emans7Tim J. M. Welting8Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, NetherlandsLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, NetherlandsLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, NetherlandsDepartment of Orthopedic Surgery, University of California Davis School of Medicine, Sacramento, CA, United StatesLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, NetherlandsLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, NetherlandsLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, NetherlandsLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, NetherlandsLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, NetherlandsThe generation of cartilage from progenitor cells for the purpose of cartilage repair is often hampered by hypertrophic differentiation of the engineered cartilaginous tissue caused by endochondral ossification. Since a healthy cartilage matrix contains high amounts of Aggrecan and COMP, we hypothesized that their supplementation in the biogel used in the generation of subperiosteal cartilage mimics the composition of the cartilage extracellular matrix environment, with beneficial properties for the engineered cartilage. Supplementation of COMP or Aggrecan was studied in vitro during chondrogenic differentiation of rabbit periosteum cells and periosteum-derived chondrocytes. Low melting agarose was supplemented with bovine Aggrecan, human recombinant COMP or vehicle and was injected between the bone and periosteum at the upper medial side of the tibia of New Zealand white rabbits. Generated subperiosteal cartilage tissue was analyzed for weight, GAG and DNA content and ALP activity. Key markers of different phases of endochondral ossification were measured by RT-qPCR. For the in vitro experiments, no significant differences in chondrogenic marker expression were detected following COMP or Aggrecan supplementation, while in vivo favorable chondrogenic marker expression was detected. Gene expression levels of hypertrophic markers as well as ALP activity were significantly decreased in the Aggrecan and COMP supplemented conditions compared to controls. The wet weight and GAG content of the in vivo generated subperiosteal cartilage tissue was not significantly different between groups. Data demonstrate the potential of Aggrecan and COMP to favorably influence the subperiosteal microenvironment for the in vivo generation of cartilage for the optimization of cartilage regenerative approaches.https://www.frontiersin.org/article/10.3389/fbioe.2020.01036/fullchondrocyte hypertrophyendochondral ossificationCOMPaggrecanperiosteumperiosteal chondrogenesis |
| spellingShingle | Marjolein M. J. Caron Maarten P. F. Janssen Laura Peeters Dominik R. Haudenschild Andy Cremers Don A. M. Surtel Lodewijk W. van Rhijn Pieter J. Emans Tim J. M. Welting Aggrecan and COMP Improve Periosteal Chondrogenesis by Delaying Chondrocyte Hypertrophic Maturation Frontiers in Bioengineering and Biotechnology chondrocyte hypertrophy endochondral ossification COMP aggrecan periosteum periosteal chondrogenesis |
| title | Aggrecan and COMP Improve Periosteal Chondrogenesis by Delaying Chondrocyte Hypertrophic Maturation |
| title_full | Aggrecan and COMP Improve Periosteal Chondrogenesis by Delaying Chondrocyte Hypertrophic Maturation |
| title_fullStr | Aggrecan and COMP Improve Periosteal Chondrogenesis by Delaying Chondrocyte Hypertrophic Maturation |
| title_full_unstemmed | Aggrecan and COMP Improve Periosteal Chondrogenesis by Delaying Chondrocyte Hypertrophic Maturation |
| title_short | Aggrecan and COMP Improve Periosteal Chondrogenesis by Delaying Chondrocyte Hypertrophic Maturation |
| title_sort | aggrecan and comp improve periosteal chondrogenesis by delaying chondrocyte hypertrophic maturation |
| topic | chondrocyte hypertrophy endochondral ossification COMP aggrecan periosteum periosteal chondrogenesis |
| url | https://www.frontiersin.org/article/10.3389/fbioe.2020.01036/full |
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