Wnt3a-Producing Fibroblasts in Ovariectomy-Induced Osteoporosis in a Rat Model

Abstract

We investigated the effect of in vitro cultured Wnt3a-producing fibroblasts on positive bone balance and regeneration of the osteopenic skeleton. Thirty-six female Wistar rats (250-300 g, aged 12 weeks) were randomized into three groups: a control group (sham-operated), ovariectomy (OVX) group, and OVX with Wnt-cell injection (OVX with Wnt) group. Wnt3a-producing fibroblasts were injected into the lateral tail vein at 2 and 4 weeks after OVX. Both tibias were removed at 5, 6, 7, and 8 weeks after OVX, and pathological and micro-CT evaluations were performed. We also evaluated beta-catenin expression by immunohistochemical staining. For bone metabolism detection, we evaluated the expression of bone alkaline phosphatase (BALP), osteocalcin, and C-telopeptide of collagen type I. Bone mineral density, trabecular bone volume, trabecular number, trabecular thickness were higher, while trabecular seperation was lower, in the OVX with Wnt group than in the OVX group. BALP and osteocalcin levels were significantly higher in the OVX with Wnt group compared to the control and OVX groups. beta-catenin expression was significantly lower in the OVX group than in the other two groups. Based on these results, we hypothesized that Wnt3a-producing fibroblasts may be effective for the induction of bone formation.