The effect of bone morphogenetic protein-2 expression on the early fate of skeletal muscle-derived cells

D. S. Musgrave; R. Pruchnic; V. Wright; P. Bosch; S. C. Ghivizzani; P. D. Robbins; J. Huard

doi:10.1016/S8756-3282(01)00413-6

The effect of bone morphogenetic protein-2 expression on the early fate of skeletal muscle-derived cells

D. S. Musgrave, R. Pruchnic, V. Wright, P. Bosch, S. C. Ghivizzani, P. D. Robbins, J. Huard

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

The identification of bone morphogenetic proteins (BMPs) has stimulated intense interest in BMP delivery approaches. Ex vivo BMP-2 gene delivery has recently been described using skeletal muscle-derived cells. Skeletal muscle-derived cells, because of proven efficient transgene delivery and osteocompetence, represent an attractive cell population on which to base ex vivo BMP-2 gene delivery. However, the early in vivo fate of BMP-2-expressing muscle-derived cells is unknown. This study investigates the in vivo effects of BMP-2 secretion on skeletal muscle-derived cells in terms of cell survival and cell differentiation. The first experiment compared survival of BMP-2-expressing cells with control cells during the first 48 h after in vivo implantation. The results demonstrate that BMP-2 secretion did not adversely affect cell survival 8, 24, or 48 h after intramuscular implantation. The second experiment histologically compared the fate of BMP-2-expressing muscle-derived cells to the same cells not expressing BMP-2. The results show that BMP-2 expression prevented in vivo myogenic differentiation and promoted osteogenic differentiation of the transduced cells. This study further supports the existence of osteoprogenitor cells residing within skeletal muscle. Moreover, it is demonstrated that BMP-2 secretion does not adversely affect early cell survival of muscle-derived cells. These data are important for future investigations into BMP-2 gene delivery approaches to the musculoskeletal system.

Original language	English (US)
Pages (from-to)	499-506
Number of pages	8
Journal	Bone
Volume	28
Issue number	5
DOIs	https://doi.org/10.1016/S8756-3282(01)00413-6
State	Published - 2001
Externally published	Yes

Bibliographical note

Funding Information:
The authors thank the Genetics Institute (Cambridge, MA) for graciously providing the rhBMP-2 plasmid and Stephen Hardy, Ph.D., for providing the Cre-Lox adenoviral system. We also thank Marcelle Pellerin and Arvydas Usas for technical help, and Megan Mowry and Dana Och for secretarial and editorial support. The work was financially supported by the Pittsburgh Tissue Engineering Initiative (PTEI), the National Institutes of Health (NIH Grant 1P60 AR44811-01), and the William F. & Jean W. Donaldson chair at Children’s Hospital of Pittsburgh.

Keywords

Adenovirus
Bone morphogenetic protein-2 (BMP-2)
Ectopic bone formation
Muscle regeneration
Muscle-derived cells
β-galactosidase

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10.1016/S8756-3282(01)00413-6

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title = "The effect of bone morphogenetic protein-2 expression on the early fate of skeletal muscle-derived cells",

abstract = "The identification of bone morphogenetic proteins (BMPs) has stimulated intense interest in BMP delivery approaches. Ex vivo BMP-2 gene delivery has recently been described using skeletal muscle-derived cells. Skeletal muscle-derived cells, because of proven efficient transgene delivery and osteocompetence, represent an attractive cell population on which to base ex vivo BMP-2 gene delivery. However, the early in vivo fate of BMP-2-expressing muscle-derived cells is unknown. This study investigates the in vivo effects of BMP-2 secretion on skeletal muscle-derived cells in terms of cell survival and cell differentiation. The first experiment compared survival of BMP-2-expressing cells with control cells during the first 48 h after in vivo implantation. The results demonstrate that BMP-2 secretion did not adversely affect cell survival 8, 24, or 48 h after intramuscular implantation. The second experiment histologically compared the fate of BMP-2-expressing muscle-derived cells to the same cells not expressing BMP-2. The results show that BMP-2 expression prevented in vivo myogenic differentiation and promoted osteogenic differentiation of the transduced cells. This study further supports the existence of osteoprogenitor cells residing within skeletal muscle. Moreover, it is demonstrated that BMP-2 secretion does not adversely affect early cell survival of muscle-derived cells. These data are important for future investigations into BMP-2 gene delivery approaches to the musculoskeletal system.",

keywords = "Adenovirus, Bone morphogenetic protein-2 (BMP-2), Ectopic bone formation, Muscle regeneration, Muscle-derived cells, β-galactosidase",

author = "Musgrave, {D. S.} and R. Pruchnic and V. Wright and P. Bosch and Ghivizzani, {S. C.} and Robbins, {P. D.} and J. Huard",

note = "Funding Information: The authors thank the Genetics Institute (Cambridge, MA) for graciously providing the rhBMP-2 plasmid and Stephen Hardy, Ph.D., for providing the Cre-Lox adenoviral system. We also thank Marcelle Pellerin and Arvydas Usas for technical help, and Megan Mowry and Dana Och for secretarial and editorial support. The work was financially supported by the Pittsburgh Tissue Engineering Initiative (PTEI), the National Institutes of Health (NIH Grant 1P60 AR44811-01), and the William F. & Jean W. Donaldson chair at Children{\textquoteright}s Hospital of Pittsburgh. ",

year = "2001",

doi = "10.1016/S8756-3282(01)00413-6",

language = "English (US)",

volume = "28",

pages = "499--506",

journal = "Bone",

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T1 - The effect of bone morphogenetic protein-2 expression on the early fate of skeletal muscle-derived cells

AU - Musgrave, D. S.

AU - Pruchnic, R.

AU - Wright, V.

AU - Bosch, P.

AU - Ghivizzani, S. C.

AU - Robbins, P. D.

AU - Huard, J.

N1 - Funding Information: The authors thank the Genetics Institute (Cambridge, MA) for graciously providing the rhBMP-2 plasmid and Stephen Hardy, Ph.D., for providing the Cre-Lox adenoviral system. We also thank Marcelle Pellerin and Arvydas Usas for technical help, and Megan Mowry and Dana Och for secretarial and editorial support. The work was financially supported by the Pittsburgh Tissue Engineering Initiative (PTEI), the National Institutes of Health (NIH Grant 1P60 AR44811-01), and the William F. & Jean W. Donaldson chair at Children’s Hospital of Pittsburgh.

PY - 2001

Y1 - 2001

N2 - The identification of bone morphogenetic proteins (BMPs) has stimulated intense interest in BMP delivery approaches. Ex vivo BMP-2 gene delivery has recently been described using skeletal muscle-derived cells. Skeletal muscle-derived cells, because of proven efficient transgene delivery and osteocompetence, represent an attractive cell population on which to base ex vivo BMP-2 gene delivery. However, the early in vivo fate of BMP-2-expressing muscle-derived cells is unknown. This study investigates the in vivo effects of BMP-2 secretion on skeletal muscle-derived cells in terms of cell survival and cell differentiation. The first experiment compared survival of BMP-2-expressing cells with control cells during the first 48 h after in vivo implantation. The results demonstrate that BMP-2 secretion did not adversely affect cell survival 8, 24, or 48 h after intramuscular implantation. The second experiment histologically compared the fate of BMP-2-expressing muscle-derived cells to the same cells not expressing BMP-2. The results show that BMP-2 expression prevented in vivo myogenic differentiation and promoted osteogenic differentiation of the transduced cells. This study further supports the existence of osteoprogenitor cells residing within skeletal muscle. Moreover, it is demonstrated that BMP-2 secretion does not adversely affect early cell survival of muscle-derived cells. These data are important for future investigations into BMP-2 gene delivery approaches to the musculoskeletal system.

AB - The identification of bone morphogenetic proteins (BMPs) has stimulated intense interest in BMP delivery approaches. Ex vivo BMP-2 gene delivery has recently been described using skeletal muscle-derived cells. Skeletal muscle-derived cells, because of proven efficient transgene delivery and osteocompetence, represent an attractive cell population on which to base ex vivo BMP-2 gene delivery. However, the early in vivo fate of BMP-2-expressing muscle-derived cells is unknown. This study investigates the in vivo effects of BMP-2 secretion on skeletal muscle-derived cells in terms of cell survival and cell differentiation. The first experiment compared survival of BMP-2-expressing cells with control cells during the first 48 h after in vivo implantation. The results demonstrate that BMP-2 secretion did not adversely affect cell survival 8, 24, or 48 h after intramuscular implantation. The second experiment histologically compared the fate of BMP-2-expressing muscle-derived cells to the same cells not expressing BMP-2. The results show that BMP-2 expression prevented in vivo myogenic differentiation and promoted osteogenic differentiation of the transduced cells. This study further supports the existence of osteoprogenitor cells residing within skeletal muscle. Moreover, it is demonstrated that BMP-2 secretion does not adversely affect early cell survival of muscle-derived cells. These data are important for future investigations into BMP-2 gene delivery approaches to the musculoskeletal system.

KW - Adenovirus

KW - Bone morphogenetic protein-2 (BMP-2)

KW - Ectopic bone formation

KW - Muscle regeneration

KW - Muscle-derived cells

KW - β-galactosidase

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DO - 10.1016/S8756-3282(01)00413-6

M3 - Article

C2 - 11344049

AN - SCOPUS:0035046975

SN - 8756-3282

VL - 28

SP - 499

EP - 506

JO - Bone

JF - Bone

IS - 5

ER -

The effect of bone morphogenetic protein-2 expression on the early fate of skeletal muscle-derived cells

Abstract

Bibliographical note

Keywords

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