Loss of scleraxis in mice leads to geometric & structural changes in cortical bone, as well as asymmetry in fracture healing

Jennifer A. Mckenzie; Evan Buettmann; Adam C. Abraham; Michael J. Gardner; Matthew J. Silva; Megan L. Killian

doi:10.1096/fj.201600969R

Loss of scleraxis in mice leads to geometric & structural changes in cortical bone, as well as asymmetry in fracture healing

Jennifer A. Mckenzie, Evan Buettmann, Adam C. Abraham, Michael J. Gardner, Matthew J. Silva, Megan L. Killian

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

14 Scopus citations

Abstract

Scleraxis (Scx) is aknownregulator of tendon development, and recentwork has identified the role of Scx in bone modeling.However, the role of Scx in fracture healing has not yet been explored. This study was conducted to identify the role of Scx in cortical bone development and fracture healing. Scx green fluorescent protein-labeled (ScxGFP) reporter and Scx-knockout (Scx-mutant) mice were used to assess bone morphometry and the effects of fracture healing on Scx localization and gene expression, aswell as callus healing response. Botulinumtoxin (BTX) was used to investigate muscle unloading effects on callus shape. Scx-mutant long bones had structural and mechanicaldefects. Scx gene expression was elevated and bmp4was decreased at 24 h after fracture. ScxGFP+ cellswere localized throughout the healing callus after fracture. Scx-mutant mice demonstrated disrupted callus healing and asymmetry. Asymmetry of Scx-mutant calluswas not due to muscle unloading.Wild-Type littermates (age matched) served as controls. This is the first study to explore the role of Scx in cortical bone mechanics and fracture healing. Deletion of Scx during development led to altered long bone properties and callus healing. This study also demonstrated that Scxmay play a role in the periosteal response during fracture healing.

Original language	English
Pages (from-to)	882-892
Number of pages	11
Journal	FASEB Journal
Volume	31
Issue number	3
DOIs	https://doi.org/10.1096/fj.201600969R
State	Published - Mar 2017

Keywords

Callus
Development
Skeletal repair
Tendon
Transcription factors

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10.1096/fj.201600969R

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title = "Loss of scleraxis in mice leads to geometric & structural changes in cortical bone, as well as asymmetry in fracture healing",

abstract = "Scleraxis (Scx) is aknownregulator of tendon development, and recentwork has identified the role of Scx in bone modeling.However, the role of Scx in fracture healing has not yet been explored. This study was conducted to identify the role of Scx in cortical bone development and fracture healing. Scx green fluorescent protein-labeled (ScxGFP) reporter and Scx-knockout (Scx-mutant) mice were used to assess bone morphometry and the effects of fracture healing on Scx localization and gene expression, aswell as callus healing response. Botulinumtoxin (BTX) was used to investigate muscle unloading effects on callus shape. Scx-mutant long bones had structural and mechanicaldefects. Scx gene expression was elevated and bmp4was decreased at 24 h after fracture. ScxGFP+ cellswere localized throughout the healing callus after fracture. Scx-mutant mice demonstrated disrupted callus healing and asymmetry. Asymmetry of Scx-mutant calluswas not due to muscle unloading.Wild-Type littermates (age matched) served as controls. This is the first study to explore the role of Scx in cortical bone mechanics and fracture healing. Deletion of Scx during development led to altered long bone properties and callus healing. This study also demonstrated that Scxmay play a role in the periosteal response during fracture healing.",

keywords = "Callus, Development, Skeletal repair, Tendon, Transcription factors",

author = "Mckenzie, {Jennifer A.} and Evan Buettmann and Abraham, {Adam C.} and Gardner, {Michael J.} and Silva, {Matthew J.} and Killian, {Megan L.}",

note = "Funding Information: This work was funded by the U.S. National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Grants F32 AR064652 (to M.L.K.), and R21 AR066798 (to M.J.S. and M.J.G.); Washington University Musculoskeletal Research Center Grant NIH-P30 AR057235; the Orthopaedic Research and Education Foundation, and the Children's Discovery Institute (Postdoctoral Fellowship to M.L.K.). The authors thank Daniel Leib and Crystal Idleburg (Musculoskeletal Research Center) for microCT and histology assistance. The authors declare no conflicts of interest.",

year = "2017",

month = mar,

doi = "10.1096/fj.201600969R",

language = "English",

volume = "31",

pages = "882--892",

journal = "FASEB Journal",

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T1 - Loss of scleraxis in mice leads to geometric & structural changes in cortical bone, as well as asymmetry in fracture healing

AU - Mckenzie, Jennifer A.

AU - Buettmann, Evan

AU - Abraham, Adam C.

AU - Gardner, Michael J.

AU - Silva, Matthew J.

AU - Killian, Megan L.

N1 - Funding Information: This work was funded by the U.S. National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Grants F32 AR064652 (to M.L.K.), and R21 AR066798 (to M.J.S. and M.J.G.); Washington University Musculoskeletal Research Center Grant NIH-P30 AR057235; the Orthopaedic Research and Education Foundation, and the Children's Discovery Institute (Postdoctoral Fellowship to M.L.K.). The authors thank Daniel Leib and Crystal Idleburg (Musculoskeletal Research Center) for microCT and histology assistance. The authors declare no conflicts of interest.

PY - 2017/3

Y1 - 2017/3

N2 - Scleraxis (Scx) is aknownregulator of tendon development, and recentwork has identified the role of Scx in bone modeling.However, the role of Scx in fracture healing has not yet been explored. This study was conducted to identify the role of Scx in cortical bone development and fracture healing. Scx green fluorescent protein-labeled (ScxGFP) reporter and Scx-knockout (Scx-mutant) mice were used to assess bone morphometry and the effects of fracture healing on Scx localization and gene expression, aswell as callus healing response. Botulinumtoxin (BTX) was used to investigate muscle unloading effects on callus shape. Scx-mutant long bones had structural and mechanicaldefects. Scx gene expression was elevated and bmp4was decreased at 24 h after fracture. ScxGFP+ cellswere localized throughout the healing callus after fracture. Scx-mutant mice demonstrated disrupted callus healing and asymmetry. Asymmetry of Scx-mutant calluswas not due to muscle unloading.Wild-Type littermates (age matched) served as controls. This is the first study to explore the role of Scx in cortical bone mechanics and fracture healing. Deletion of Scx during development led to altered long bone properties and callus healing. This study also demonstrated that Scxmay play a role in the periosteal response during fracture healing.

AB - Scleraxis (Scx) is aknownregulator of tendon development, and recentwork has identified the role of Scx in bone modeling.However, the role of Scx in fracture healing has not yet been explored. This study was conducted to identify the role of Scx in cortical bone development and fracture healing. Scx green fluorescent protein-labeled (ScxGFP) reporter and Scx-knockout (Scx-mutant) mice were used to assess bone morphometry and the effects of fracture healing on Scx localization and gene expression, aswell as callus healing response. Botulinumtoxin (BTX) was used to investigate muscle unloading effects on callus shape. Scx-mutant long bones had structural and mechanicaldefects. Scx gene expression was elevated and bmp4was decreased at 24 h after fracture. ScxGFP+ cellswere localized throughout the healing callus after fracture. Scx-mutant mice demonstrated disrupted callus healing and asymmetry. Asymmetry of Scx-mutant calluswas not due to muscle unloading.Wild-Type littermates (age matched) served as controls. This is the first study to explore the role of Scx in cortical bone mechanics and fracture healing. Deletion of Scx during development led to altered long bone properties and callus healing. This study also demonstrated that Scxmay play a role in the periosteal response during fracture healing.

KW - Callus

KW - Development

KW - Skeletal repair

KW - Tendon

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=85014545266&partnerID=8YFLogxK

U2 - 10.1096/fj.201600969R

DO - 10.1096/fj.201600969R

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AN - SCOPUS:85014545266

SN - 0892-6638

VL - 31

SP - 882

EP - 892

JO - FASEB Journal

JF - FASEB Journal

IS - 3

ER -

Loss of scleraxis in mice leads to geometric & structural changes in cortical bone, as well as asymmetry in fracture healing

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