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Pro-osteogenic Effects of WNT in a Mouse Model of Bone Formation Around Femoral Implants.
Li, Zhijun; Yuan, Xue; Arioka, Masaki; Bahat, Daniel; Sun, Qiang; Chen, Jinlong; Helms, Jill A.
Afiliación
  • Li Z; Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 300052, China.
  • Yuan X; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, 94305, USA.
  • Arioka M; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, 94305, USA.
  • Bahat D; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, 94305, USA.
  • Sun Q; Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
  • Chen J; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
  • Helms JA; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, 94305, USA.
Calcif Tissue Int ; 108(2): 240-251, 2021 02.
Article en En | MEDLINE | ID: mdl-32990765
Wnt signaling maintains homeostasis in the bone marrow cavity: if Wnt signaling is inhibited then bone volume and density would decline. In this study, we identified a population of Wnt-responsive cells as osteoprogenitor in the intact trabecular bone region, which were responsible for bone development and turnover. If an implant was placed into the long bone, this Wnt-responsive population and their progeny contributed to osseointegration. We employed Axin2CreCreERT2/+;R26mTmG/+ transgenic mouse strain in which Axin2-positive, Wnt-responsive cells, and their progeny are permanently labeled by GFP upon exposure to tamoxifen. Each mouse received femoral implants placed into a site prepared solely by drilling, and a single-dose liposomal WNT3A protein was used in the treatment group. A lineage tracing strategy design allowed us to identify cells actively expressing Axin2 in response to Wnt signaling pathway. These tools demonstrated that Wnt-responsive cells and their progeny comprise a quiescent population residing in the trabecular region. In response to an implant placed, this population becomes mitotically active: cells migrated into the peri-implant region, up-regulated the expression of osteogenic proteins. Ultimately, those cells gave rise to osteoblasts that produced significantly more new bone in the peri-implant region. Wnt-responsive cells directly contributed to implant osseointegration. Using a liposomal WNT3A protein therapeutic, we showed that a single application at the time of implant placed was sufficient to accelerate osseointegration. The Wnt-responsive cell population in trabecular bone, activated by injury, ultimately contributes to implant osseointegration. Liposomal WNT3A protein therapeutic accelerates implant osseointegration in the long bone.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Prótesis e Implantes / Oseointegración / Proteína Wnt3A Límite: Animals Idioma: En Revista: Calcif Tissue Int Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Prótesis e Implantes / Oseointegración / Proteína Wnt3A Límite: Animals Idioma: En Revista: Calcif Tissue Int Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos