Abstract
Notch induces Hairy and Enhancer of Split-related with YRPW motif (Hey)1, Hey2, and HeyL expression in osteoblasts, but the contributions of these genes to the skeletal effects of Notch are not fully understood. HEY1 misexpression has limited skeletal impact, female HeyL null mice display increased bone mass, and Hey2 inactivation is developmentally lethal. To inactivate Hey2 in immature or mature osteoblasts, Hey2(loxP/loxP) mice were crossed with transgenics expressing CRE under the control of the osterix (Osx-Cre) or osteocalcin (Oc-Cre) promoters to generate Osx-Cre(+/-);Hey2(Δ/Δ) or Oc-Cre(+/-);Hey2(Δ/Δ) mice. Trabecular bone volume increased in 3-month-old Osx-Cre(+/-);Hey2(Δ/Δ) and Oc-Cre(+/-);Hey2(Δ/Δ) male mice and in 1-month-old Oc-Cre(+/-);Hey2(Δ/Δ) female mice, although 3-month-old Oc-Cre(+/-);Hey2(Δ/Δ) females developed osteopenia. Alkaline phosphatase liver/bone/kidney (ALPL) expression and activity were suppressed in osteoblasts from Oc-Cre(+/-);Hey2(Δ/Δ) mice of both sexes. To overexpress HEY2 in osteoblasts, transgenic mice where a 3.6-kb fragment of the rat collagen type-I α1 promoter directs HEY2 expression were created. Three-month-old Hey2 transgenic males exhibited decreased osteoblast activity and increased bone resorption and developed osteopenia at 6 months of age. Hey2 transgenic females exhibited reduced osteoblast number and function, but no changes in bone resorption. HEY2 overexpression in osteoblasts from mice of both sexes inhibited ALPL expression and activity and suppressed osteocalcin transcripts in cells from male mice only. HEY2 overexpression in osteoblasts from male mice enhanced bone resorption by co-cultured splenocytes and induced interleukin-6, a molecule that promotes osteoclastogenesis. In conclusion, HEY2 decreases skeletal mass and regulates bone remodeling in male mice.
Highlights
There was a stronger correlation with the chronic inflammatory cell infiltrate (r = 0.53; p < 0.0001) and the density of H pylori colonisation (r = 0.54; p < 0.0001)
Paired antral and corpus biopsies were obtained from 28 patients
We found no correlation between patient age and antral labelling index (r = 0.13; p = 0.35)
Summary
To determine if there is a correlation between the histological findings in the gastric mucosa and the degree of cell proliferation in gastric antral biopsies
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have