Vitamin C deficiency accelerates bone loss inducing an increase in PPAR-γ expression in SMP30 knockout mice

Abstract

Senescence marker protein (SMP) 30 knockout (KO) mice display symptoms of scurvy, including spontaneous bone fractures, and this was considered to be induced by a failure of collagen synthesis owing to vitamin C deficiency. However, low bone mineral density is also known to be associated with spontaneous bone fracture. Therefore, we investigated the effects of vitamin C deficiency on the balance between osteoblasts and osteoclasts in SMP30 KO mice as evidenced by histopathology. All mice were fed a vitamin C-free diet, and only one group (KV) mice were given water containing 1.5 g/l of vitamin C, whereas wild-type (WT) and KO mice were given normal drinking tap water without vitamin C for 16 weeks. After 16 weeks, all femur samples were removed for histopathological examination. The femurs of KO mice showed significantly reduced bone area and decreased number of osteoblasts compared with those of WT mice and KV mice. KO mice also exhibited the lowest level of alkaline phosphatase (ALP) expression in their femurs. However, KO mice showed the most elevated expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Moreover, KO mice had the strongest peroxisome proliferator-activated receptor (PPAR)-γ expression level in their osteoblasts and the highest number of TUNEL-positive bone marrow cells. Therefore, we concluded that vitamin C deficiency plays an important role in spontaneous bone fracture by inhibiting osteoblast differentiation and promoting transition of osteoblasts to adipocytes, and this could in turn be related to the increased PPAR-γ expression.