Enhanced matrix synthesis and in vitro formation of cartilage-like tissue by genetically modified chondrocytes expressing BMP-7

Chisa Hidaka, Mannix Quitoriano, Russell F. Warren, Ronald Crystal

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Bone morphogenic protein-7 (BMP-7) supports ectopic cartilage and bone formation, is expressed in normal articular cartilage, and increases matrix synthesis in chondrocytes. Based on this knowledge, we hypothesized that an adenovirus (Ad) vector encoding human BMP-7 could be used to modify chondrocytes genetically to improve their capacity for cartilage repair. An adenovirus vector encoding BMP-7 (AdBMP-7) was constructed and its bioactivity confirmed by ectopic bone formation assay. AdBMP-7 modification of bovine chondrocytes induced expression of BMP-7 mRNA and bioactive protein, resulting in an increase in incorporation of 35SO-4 into proteoglycan, 3H-proline uptake into protein, and the expression of the cartilage-specific matrix genes, aggrecan and type II collagen. An in vitro model of chondrocyte transplantation was used to demonstrate the feasibility of using genetically modified chondrocytes to enhance formation of cartilage-like tissue. When transplanted onto cartilage explants and maintained in vitro for 3 weeks, chondrocytes modified with AdBMP-7 formed 1.9-fold thicker tissue than chondrocytes modified with a control vector (P < 0.001). This tissue was positive for type II collagen and proteoglycan but negative for type X collagen and demonstrated a cartilage-like morphology. These observations suggest that Ad-mediated transfer of BMP-7 gene to chondrocytes enhances the chondrocyte-specific matrix synthesis and their capacity to form cartilage-like tissue, thus representing a strategy that may improve cell-based cartilage repair.

Original languageEnglish
Pages (from-to)751-758
Number of pages8
JournalJournal of Orthopaedic Research
Volume19
Issue number5
DOIs
Publication statusPublished - 11 Sep 2001
Externally publishedYes

Fingerprint

Chondrocytes
Cartilage
Bone and Bones
Adenoviridae
Proteins
Bone Morphogenetic Protein 7
Collagen Type II
Proteoglycans
Osteogenesis
Collagen Type X
In Vitro Techniques
Aggrecans
Articular Cartilage
Proline
Transplantation
Messenger RNA

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Enhanced matrix synthesis and in vitro formation of cartilage-like tissue by genetically modified chondrocytes expressing BMP-7. / Hidaka, Chisa; Quitoriano, Mannix; Warren, Russell F.; Crystal, Ronald.

In: Journal of Orthopaedic Research, Vol. 19, No. 5, 11.09.2001, p. 751-758.

Research output: Contribution to journalArticle

@article{e33e20e5b357434e900d6113ad51a7d0,
title = "Enhanced matrix synthesis and in vitro formation of cartilage-like tissue by genetically modified chondrocytes expressing BMP-7",
abstract = "Bone morphogenic protein-7 (BMP-7) supports ectopic cartilage and bone formation, is expressed in normal articular cartilage, and increases matrix synthesis in chondrocytes. Based on this knowledge, we hypothesized that an adenovirus (Ad) vector encoding human BMP-7 could be used to modify chondrocytes genetically to improve their capacity for cartilage repair. An adenovirus vector encoding BMP-7 (AdBMP-7) was constructed and its bioactivity confirmed by ectopic bone formation assay. AdBMP-7 modification of bovine chondrocytes induced expression of BMP-7 mRNA and bioactive protein, resulting in an increase in incorporation of 35SO-4 into proteoglycan, 3H-proline uptake into protein, and the expression of the cartilage-specific matrix genes, aggrecan and type II collagen. An in vitro model of chondrocyte transplantation was used to demonstrate the feasibility of using genetically modified chondrocytes to enhance formation of cartilage-like tissue. When transplanted onto cartilage explants and maintained in vitro for 3 weeks, chondrocytes modified with AdBMP-7 formed 1.9-fold thicker tissue than chondrocytes modified with a control vector (P < 0.001). This tissue was positive for type II collagen and proteoglycan but negative for type X collagen and demonstrated a cartilage-like morphology. These observations suggest that Ad-mediated transfer of BMP-7 gene to chondrocytes enhances the chondrocyte-specific matrix synthesis and their capacity to form cartilage-like tissue, thus representing a strategy that may improve cell-based cartilage repair.",
author = "Chisa Hidaka and Mannix Quitoriano and Warren, {Russell F.} and Ronald Crystal",
year = "2001",
month = "9",
day = "11",
doi = "10.1016/S0736-0266(01)00019-5",
language = "English",
volume = "19",
pages = "751--758",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Enhanced matrix synthesis and in vitro formation of cartilage-like tissue by genetically modified chondrocytes expressing BMP-7

AU - Hidaka, Chisa

AU - Quitoriano, Mannix

AU - Warren, Russell F.

AU - Crystal, Ronald

PY - 2001/9/11

Y1 - 2001/9/11

N2 - Bone morphogenic protein-7 (BMP-7) supports ectopic cartilage and bone formation, is expressed in normal articular cartilage, and increases matrix synthesis in chondrocytes. Based on this knowledge, we hypothesized that an adenovirus (Ad) vector encoding human BMP-7 could be used to modify chondrocytes genetically to improve their capacity for cartilage repair. An adenovirus vector encoding BMP-7 (AdBMP-7) was constructed and its bioactivity confirmed by ectopic bone formation assay. AdBMP-7 modification of bovine chondrocytes induced expression of BMP-7 mRNA and bioactive protein, resulting in an increase in incorporation of 35SO-4 into proteoglycan, 3H-proline uptake into protein, and the expression of the cartilage-specific matrix genes, aggrecan and type II collagen. An in vitro model of chondrocyte transplantation was used to demonstrate the feasibility of using genetically modified chondrocytes to enhance formation of cartilage-like tissue. When transplanted onto cartilage explants and maintained in vitro for 3 weeks, chondrocytes modified with AdBMP-7 formed 1.9-fold thicker tissue than chondrocytes modified with a control vector (P < 0.001). This tissue was positive for type II collagen and proteoglycan but negative for type X collagen and demonstrated a cartilage-like morphology. These observations suggest that Ad-mediated transfer of BMP-7 gene to chondrocytes enhances the chondrocyte-specific matrix synthesis and their capacity to form cartilage-like tissue, thus representing a strategy that may improve cell-based cartilage repair.

AB - Bone morphogenic protein-7 (BMP-7) supports ectopic cartilage and bone formation, is expressed in normal articular cartilage, and increases matrix synthesis in chondrocytes. Based on this knowledge, we hypothesized that an adenovirus (Ad) vector encoding human BMP-7 could be used to modify chondrocytes genetically to improve their capacity for cartilage repair. An adenovirus vector encoding BMP-7 (AdBMP-7) was constructed and its bioactivity confirmed by ectopic bone formation assay. AdBMP-7 modification of bovine chondrocytes induced expression of BMP-7 mRNA and bioactive protein, resulting in an increase in incorporation of 35SO-4 into proteoglycan, 3H-proline uptake into protein, and the expression of the cartilage-specific matrix genes, aggrecan and type II collagen. An in vitro model of chondrocyte transplantation was used to demonstrate the feasibility of using genetically modified chondrocytes to enhance formation of cartilage-like tissue. When transplanted onto cartilage explants and maintained in vitro for 3 weeks, chondrocytes modified with AdBMP-7 formed 1.9-fold thicker tissue than chondrocytes modified with a control vector (P < 0.001). This tissue was positive for type II collagen and proteoglycan but negative for type X collagen and demonstrated a cartilage-like morphology. These observations suggest that Ad-mediated transfer of BMP-7 gene to chondrocytes enhances the chondrocyte-specific matrix synthesis and their capacity to form cartilage-like tissue, thus representing a strategy that may improve cell-based cartilage repair.

UR - http://www.scopus.com/inward/record.url?scp=0034858445&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034858445&partnerID=8YFLogxK

U2 - 10.1016/S0736-0266(01)00019-5

DO - 10.1016/S0736-0266(01)00019-5

M3 - Article

VL - 19

SP - 751

EP - 758

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 5

ER -