WNT3A accelerates delayed alveolar bone repair in ovariectomized mice

Osteoporos Int. 2019 Sep;30(9):1873-1885. doi: 10.1007/s00198-019-05071-x. Epub 2019 Jul 23.

Abstract

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.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Alveolar bone; Osteoporosis; Ovariectomy; Regeneration; WNT3A.

MeSH terms

  • Aging / physiology
  • Alveolar Bone Loss / diagnostic imaging
  • Alveolar Bone Loss / drug therapy
  • Alveolar Bone Loss / etiology
  • Alveolar Bone Loss / physiopathology
  • Animals
  • Bone Regeneration / drug effects*
  • Bone Resorption / physiopathology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Female
  • Maxilla / drug effects
  • Maxilla / physiology
  • Mice, Inbred BALB C
  • Molar / surgery
  • Osteogenesis / physiology
  • Osteoporosis / complications
  • Osteoporosis / physiopathology*
  • Ovariectomy
  • Tooth Extraction
  • Tooth Socket / diagnostic imaging
  • Tooth Socket / drug effects*
  • Tooth Socket / physiology
  • Wnt3A Protein / pharmacology*
  • Wound Healing / drug effects
  • X-Ray Microtomography / methods

Substances

  • WNT3A protein, human
  • Wnt3A Protein