Bone Degeneration and Its Recovery in SMP30/GNL-Knockout Mice

J Nutr Health Aging. 2017;21(5):573-578. doi: 10.1007/s12603-016-0841-8.


Senescence marker protein-30 (SMP30) decreases androgen-independently with aging and is a lactone-hydrolyzing enzyme gluconolactonase (GNL) that is involved in vitamin C biosynthesis. In the present study, bone properties of SMP30/GNL knockout (KO) mice with deficiency in vitamin C synthesis were investigated to reveal the effects of SMP30/GNL and exogenous vitamin C supplementation on bone formation. Mineral content (BMC) and mineral density (BMD) of the mandible and femur of SMP30/GNL KO and wild-type mice at 2 and 3 months of age with or without vitamin C supplementation were measured by dual-energy X-ray absorptiometry. Body and bone weight of both age groups decreased and became significantly lower than those of wild-type mice. The bones of SMP30/GNL KO mice were rough and porous, with BMC and BMD significantly below wild-type. Oral supplementation with vitamin C eliminated differences in body weight, bone weight, BMC, and BMD between SMP30/GNL KO and wild-type mice at each age. These results indicate that bone degeneration in SMP30/GNL KO mice was caused by lack of vitamin C, and that this mouse strain is an appropriate model for bone metabolism in humans, which have no ability to synthesize vitamin C.

Keywords: Vitamin C; animal model; bone mineral density; bone mineral ratio; femur; mandible.

MeSH terms

  • Absorptiometry, Photon
  • Aging
  • Animals
  • Ascorbic Acid / biosynthesis*
  • Ascorbic Acid / metabolism
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use
  • Ascorbic Acid Deficiency / complications*
  • Ascorbic Acid Deficiency / metabolism
  • Body Weight / drug effects
  • Bone Density / drug effects*
  • Bone Diseases, Metabolic / etiology*
  • Bone Diseases, Metabolic / metabolism
  • Calcium-Binding Proteins / metabolism*
  • Carboxylic Ester Hydrolases / metabolism*
  • Dietary Supplements
  • Disease Models, Animal
  • Female
  • Femur / drug effects
  • Femur / metabolism
  • Femur / pathology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mandible / drug effects
  • Mandible / metabolism
  • Mandible / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoporosis / drug therapy
  • Osteoporosis / metabolism
  • Osteoporosis / pathology


  • Calcium-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Rgn protein, mouse
  • Carboxylic Ester Hydrolases
  • gluconolactonase
  • Ascorbic Acid