Osteoporosis International

, Volume 30, Issue 9, pp 1873–1885 | Cite as

WNT3A accelerates delayed alveolar bone repair in ovariectomized mice

  • Y. Liu
  • Z. Li
  • M. Arioka
  • L. Wang
  • C. Bao
  • J.A. HelmsEmail author
Original Article



Our goal was to evaluate alveolar bone healing in OVX mice, and to assess the functional utility of a WNT-based treatment to accelerate healing in mice with an osteoporotic-like bony phenotype.


Is osteoporosis a risk factor for dental procedures? This relatively simple question is exceedingly difficult to answer in a clinical setting, for two reasons. First, as an age-related disease, osteoporosis is frequently accompanied by age-related co-morbidities that can contribute to slower tissue repair. Second, the intervals at which alveolar bone repair are assessed in a clinical study are often measured in months to years. This study aimed to evaluate alveolar bone repair in ovariectomized (OVX) mice and provide preclinical evidence to support a WNT-based treatment to accelerate alveolar bone formation.


OVX was performed in young mice to produce an osteoporotic-like bone phenotype. Thereafter, the rate of extraction socket healing and osteotomy repair was assessed. A liposomal WNT3A treatment was tested for its ability to promote alveolar bone formation in this OVX-induced model of bone loss.


Bone loss was observed throughout the murine skeleton, including the maxilla, and mirrored the pattern of bone loss observed in aged mice. Injuries to the alveolar bone, including tooth extraction and osteotomy site preparation, both healed significantly slower than the same injuries produced in young controls. Given sufficient time, however, all injuries eventually healed. In OVX mice, osteotomies healed significantly faster if they were treated with L-WNT3A.


Alveolar bone injuries heal slower in OVX mice that exhibit an osteoporotic-like phenotype. The rate of alveolar bone repair in OVX mice can be significantly promoted with local delivery of L-WNT3A.


Alveolar bone Osteoporosis Ovariectomy Regeneration WNT3A 



We thank Bo Liu, Xue Yuan, Xiaohui Zhang, and Quanchen Xu for their invaluable help with histology and data analysis.

Funding information

This research project was supported by a grant from the National Institutes of Health (R01DE024000-11, J.A.H.), a grant from the National Key Research and Development Program of China (2016YFC1102702; L.W. and C.B.), and a grant from the National Natural Science Foundation of China (81600910; L.W.). Salary support for Y.L. was provided by L.W. and C.B. Funding to support this research was provided by J.A.H.

Compliance with ethical standards

The Stanford Committee on Animal Research approved all procedures, which conform to ARRIVE guidelines.

Conflicts of interest



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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  • Y. Liu
    • 1
    • 2
  • Z. Li
    • 2
    • 3
  • M. Arioka
    • 2
    • 4
  • L. Wang
    • 1
  • C. Bao
    • 1
  • J.A. Helms
    • 2
    Email author
  1. 1.State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
  2. 2.Division of Plastic and Reconstructive Surgery, Department of SurgeryStanford University School of MedicinePalo AltoUSA
  3. 3.Department of OrthopedicsTianjin Medical University General HospitalTianjinChina
  4. 4.Department of Clinical Pharmacology, Faculty of Medical SciencesKyushu UniversityFukuokaJapan

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