The ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing

Xuanyu Lu, Wenjin Li, Satoshi Fukumoto, Yoshihiko Yamada, Carla A. Evans, Tom Diekwisch, Xianghong Luan

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

抄録

The extracellular matrix (ECM) provides structural support, cell migration anchorage, cell differentiation cues, and fine-tuned cell proliferation signals during all stages of bone fracture healing, including cartilaginous callus formation, callus remodeling, and bony bridging of the fracture gap. In the present study we have defined the role of the extracellular matrix protein ameloblastin (AMBN) in fracture resistance and fracture healing of mouse long bones. To this end, long bones from WT and AMBN δ5-6 truncation model mice were subjected to biomechanical analysis, fracture healing assays, and stem cell colony formation comparisons. The effect of exogenous AMBN addition to fracture sites was also determined. Our data indicate that lack of a functional AMBN in the bone matrix resulted in 31% decreased femur bone mass and 40% reduced energy to failure. On a cellular level, AMBN function inhibition diminished the proliferative capacity of fracture repair callus cells, as evidenced by a 58% reduction in PCNA and a 40% reduction in Cyclin D1 gene expression, as well as PCNA immunohistochemistry. In terms of fracture healing, AMBN truncation was associated with an enhanced and prolonged chondrogenic phase, resulting in delayed mineralized tissue gene expression and delayed ossification of the fracture repair callus. Underscoring a role of AMBN in fracture healing, there was a 6.9-fold increase in AMBN expression at the fracture site one week after fracture, and distinct AMBN immunolabeling in the fracture gap. Finally, application of exogenous AMBN protein to bone fracture sites accelerated callus formation and bone fracture healing (33% increase in bone volume and 19% increase in bone mineral density), validating the findings of our AMBN loss of function studies. Together, these data demonstrate the functional importance of the AMBN extracellular matrix protein in bone fracture prevention and rapid fracture healing.

元の言語英語
ページ(範囲)113-126
ページ数14
ジャーナルMatrix Biology
52-54
DOI
出版物ステータス出版済み - 5 1 2016

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Fracture Healing
Bone Fractures
Extracellular Matrix
Bony Callus
Bone and Bones
Extracellular Matrix Proteins
Proliferating Cell Nuclear Antigen
bcl-1 Genes
Colony-Forming Units Assay
Gene Expression
Bone Matrix
Osteogenesis
Bone Density
Femur
Cell Movement
Cues
Cell Differentiation
Immunohistochemistry
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Molecular Biology

これを引用

The ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing. / Lu, Xuanyu; Li, Wenjin; Fukumoto, Satoshi; Yamada, Yoshihiko; Evans, Carla A.; Diekwisch, Tom; Luan, Xianghong.

:: Matrix Biology, 巻 52-54, 01.05.2016, p. 113-126.

研究成果: ジャーナルへの寄稿記事

Lu, Xuanyu ; Li, Wenjin ; Fukumoto, Satoshi ; Yamada, Yoshihiko ; Evans, Carla A. ; Diekwisch, Tom ; Luan, Xianghong. / The ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing. :: Matrix Biology. 2016 ; 巻 52-54. pp. 113-126.
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title = "The ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing",
abstract = "The extracellular matrix (ECM) provides structural support, cell migration anchorage, cell differentiation cues, and fine-tuned cell proliferation signals during all stages of bone fracture healing, including cartilaginous callus formation, callus remodeling, and bony bridging of the fracture gap. In the present study we have defined the role of the extracellular matrix protein ameloblastin (AMBN) in fracture resistance and fracture healing of mouse long bones. To this end, long bones from WT and AMBN δ5-6 truncation model mice were subjected to biomechanical analysis, fracture healing assays, and stem cell colony formation comparisons. The effect of exogenous AMBN addition to fracture sites was also determined. Our data indicate that lack of a functional AMBN in the bone matrix resulted in 31{\%} decreased femur bone mass and 40{\%} reduced energy to failure. On a cellular level, AMBN function inhibition diminished the proliferative capacity of fracture repair callus cells, as evidenced by a 58{\%} reduction in PCNA and a 40{\%} reduction in Cyclin D1 gene expression, as well as PCNA immunohistochemistry. In terms of fracture healing, AMBN truncation was associated with an enhanced and prolonged chondrogenic phase, resulting in delayed mineralized tissue gene expression and delayed ossification of the fracture repair callus. Underscoring a role of AMBN in fracture healing, there was a 6.9-fold increase in AMBN expression at the fracture site one week after fracture, and distinct AMBN immunolabeling in the fracture gap. Finally, application of exogenous AMBN protein to bone fracture sites accelerated callus formation and bone fracture healing (33{\%} increase in bone volume and 19{\%} increase in bone mineral density), validating the findings of our AMBN loss of function studies. Together, these data demonstrate the functional importance of the AMBN extracellular matrix protein in bone fracture prevention and rapid fracture healing.",
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AU - Fukumoto, Satoshi

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AU - Evans, Carla A.

AU - Diekwisch, Tom

AU - Luan, Xianghong

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AB - The extracellular matrix (ECM) provides structural support, cell migration anchorage, cell differentiation cues, and fine-tuned cell proliferation signals during all stages of bone fracture healing, including cartilaginous callus formation, callus remodeling, and bony bridging of the fracture gap. In the present study we have defined the role of the extracellular matrix protein ameloblastin (AMBN) in fracture resistance and fracture healing of mouse long bones. To this end, long bones from WT and AMBN δ5-6 truncation model mice were subjected to biomechanical analysis, fracture healing assays, and stem cell colony formation comparisons. The effect of exogenous AMBN addition to fracture sites was also determined. Our data indicate that lack of a functional AMBN in the bone matrix resulted in 31% decreased femur bone mass and 40% reduced energy to failure. On a cellular level, AMBN function inhibition diminished the proliferative capacity of fracture repair callus cells, as evidenced by a 58% reduction in PCNA and a 40% reduction in Cyclin D1 gene expression, as well as PCNA immunohistochemistry. In terms of fracture healing, AMBN truncation was associated with an enhanced and prolonged chondrogenic phase, resulting in delayed mineralized tissue gene expression and delayed ossification of the fracture repair callus. Underscoring a role of AMBN in fracture healing, there was a 6.9-fold increase in AMBN expression at the fracture site one week after fracture, and distinct AMBN immunolabeling in the fracture gap. Finally, application of exogenous AMBN protein to bone fracture sites accelerated callus formation and bone fracture healing (33% increase in bone volume and 19% increase in bone mineral density), validating the findings of our AMBN loss of function studies. Together, these data demonstrate the functional importance of the AMBN extracellular matrix protein in bone fracture prevention and rapid fracture healing.

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