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Developmental cues for bone formation from parathyroid hormone and parathyroid hormone-related protein in an ex vivo organotypic culture system of embryonic chick femora

Developmental cues for bone formation from parathyroid hormone and parathyroid hormone-related protein in an ex vivo organotypic culture system of embryonic chick femora
Developmental cues for bone formation from parathyroid hormone and parathyroid hormone-related protein in an ex vivo organotypic culture system of embryonic chick femora
Enhancement and application of our understanding of skeletal developmental biology is critical to developing tissue engineering approaches to bone repair. We propose that use of the developing embryonic femur as a model to further understand skeletogenesis, and the effects of key differentiation agents, will aid our understanding of the developing bone niche and inform bone reparation. We have used a three-dimensional organotypic culture system of embryonic chick femora to investigate the effects of two key skeletal differentiation agents, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP), on bone and cartilage development, using a combination of microcomputed tomography and histological analysis to assess tissue formation and structure, and cellular behavior. Stimulation of embryonic day 11 (E11) organotypic femur cultures with PTH and PTHrP initiated osteogenesis. Bone formation was enhanced, with increased collagen I and STRO-1 expression, and cartilage was reduced, with decreased chondrocyte proliferation, collagen II expression, and glycosaminoglycan levels. This study demonstrates the successful use of organotypic chick femur cultures as a model for bone development, evidenced by the ability of exogenous bioactive molecules to differentially modulate bone and cartilage formation. The organotypic model outlined provides a tool for analyzing key temporal stages of bone and cartilage development, providing a paradigm for translation of bone development to improve scaffolds and skeletal stem cell treatments for skeletal regenerative medicine.
1937-3384
984-994
Smith, Emma L.
a5cfde95-6ee5-41df-a21c-a3df3fcd92ec
Kanczler, Janos M.
7e06be24-613a-42dd-9d78-1079ecd5553d
Roberts, Carol A.
4a1288ab-f13f-42c2-b838-6946946e0953
Oreffo, Richard O. C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Smith, Emma L.
a5cfde95-6ee5-41df-a21c-a3df3fcd92ec
Kanczler, Janos M.
7e06be24-613a-42dd-9d78-1079ecd5553d
Roberts, Carol A.
4a1288ab-f13f-42c2-b838-6946946e0953
Oreffo, Richard O. C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778

Smith, Emma L., Kanczler, Janos M., Roberts, Carol A. and Oreffo, Richard O. C. (2012) Developmental cues for bone formation from parathyroid hormone and parathyroid hormone-related protein in an ex vivo organotypic culture system of embryonic chick femora. Tissue Engineering Part C Methods, 18 (12), 984-994. (doi:10.1089/ten.tec.2012.0132). (PMID:22690868)

Record type: Article

Abstract

Enhancement and application of our understanding of skeletal developmental biology is critical to developing tissue engineering approaches to bone repair. We propose that use of the developing embryonic femur as a model to further understand skeletogenesis, and the effects of key differentiation agents, will aid our understanding of the developing bone niche and inform bone reparation. We have used a three-dimensional organotypic culture system of embryonic chick femora to investigate the effects of two key skeletal differentiation agents, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP), on bone and cartilage development, using a combination of microcomputed tomography and histological analysis to assess tissue formation and structure, and cellular behavior. Stimulation of embryonic day 11 (E11) organotypic femur cultures with PTH and PTHrP initiated osteogenesis. Bone formation was enhanced, with increased collagen I and STRO-1 expression, and cartilage was reduced, with decreased chondrocyte proliferation, collagen II expression, and glycosaminoglycan levels. This study demonstrates the successful use of organotypic chick femur cultures as a model for bone development, evidenced by the ability of exogenous bioactive molecules to differentially modulate bone and cartilage formation. The organotypic model outlined provides a tool for analyzing key temporal stages of bone and cartilage development, providing a paradigm for translation of bone development to improve scaffolds and skeletal stem cell treatments for skeletal regenerative medicine.

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More information

e-pub ahead of print date: 13 September 2012
Published date: 6 November 2012
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 345790
URI: http://eprints.soton.ac.uk/id/eprint/345790
ISSN: 1937-3384
PURE UUID: bc823f6d-aaff-4376-96f5-d7bb990a2b10
ORCID for Richard O. C. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

Catalogue record

Date deposited: 03 Dec 2012 15:55
Last modified: 15 Mar 2024 03:03

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Contributors

Author: Emma L. Smith
Author: Janos M. Kanczler
Author: Carol A. Roberts

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