Periosteal BMP2 activity drives bone graft healing

Chappuis, Vivianne; Gamer, Laura; Cox, Karen; Lowery, Jonathan W; Bosshardt, Dieter; Rosen, Vicki (2012). Periosteal BMP2 activity drives bone graft healing. Bone, 51(4), pp. 800-809. New York, N.Y.: Elsevier 10.1016/j.bone.2012.07.017

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Bone graft incorporation depends on the orchestrated activation of numerous growth factors and cytokines in both the host and the graft. Prominent in this signaling cascade is BMP2. Although BMP2 is dispensable for bone formation, it is required for the initiation of bone repair; thus understanding the cellular mechanisms underlying bone regeneration driven by BMP2 is essential for improving bone graft therapies. In the present study, we assessed the role of Bmp2 in bone graft incorporation using mice in which Bmp2 has been removed from the limb prior to skeletal formation (Bmp2(cKO)). When autograft transplantations were performed in Bmp2cKO mice, callus formation and bone healing were absent. Transplantation of either a vital wild type (WT) bone graft into a Bmp2(cKO) host or a vital Bmp2(cKO) graft into a WT host also resulted in the inhibition of bone graft incorporation. Histological analyses of these transplants show that in the absence of BMP2, periosteal progenitors remain quiescent and healing is not initiated. When we analyzed the expression of Sox9, a marker of chondrogenesis, on the graft surface, we found it significantly reduced when BMP2 was absent in either the graft itself or the host, suggesting that local BMP2 levels drive periosteal cell condensation and subsequent callus cell differentiation. The lack of integrated healing in the absence of BMP2 was not due to the inability of periosteal cells to respond to BMP2. Healing was achieved when grafts were pre-soaked in rhBMP2 protein, indicating that periosteal progenitors remain responsive in the absence of BMP2. In contrast to the requirement for BMP2 in periosteal progenitor activation in vital bone grafts, we found that bone matrix-derived BMP2 does not significantly enhance bone graft incorporation. Taken together, our data show that BMP2 signaling is not essential for the maintenance of periosteal progenitors, but is required for the activation of these progenitors and their subsequent differentiation along the osteo-chondrogenic pathway. These results indicate that BMP2 will be among the signaling molecules whose presence will determine success or failure of new bone graft strategies.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > Department of Periodontology
04 Faculty of Medicine > School of Dental Medicine > Department of Oral Surgery and Stomatology

UniBE Contributor:

Chappuis, Vivianne and Bosshardt, Dieter

Subjects:

600 Technology > 610 Medicine & health

ISSN:

8756-3282

Publisher:

Elsevier

Language:

English

Submitter:

Eveline Carmen Schuler

Date Deposited:

04 Oct 2013 14:30

Last Modified:

25 Jan 2017 12:15

Publisher DOI:

10.1016/j.bone.2012.07.017

PubMed ID:

22846673

Web of Science ID:

000308730200023

BORIS DOI:

10.7892/boris.11343

URI:

https://boris.unibe.ch/id/eprint/11343 (FactScience: 217438)

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