Overexpression of miR-125b in osteoblasts inhibits bone resorption without affecting skeletal development and improves age-related changes in bone mass and quality

概要

Doctoral dissertation

Overexpression of miR-125b in osteoblasts inhibits bone
resorption without affecting skeletal development and improves
age-related changes in bone mass and quality
（miR-125b の骨芽細胞特異的過剰発現は骨格成長への影響なく骨吸収
を阻害し、加齢性の骨量や骨質への変化を改善する）

Shota Ito
Biomedical Sciences Major, Doctoral Course
Graduate School of Biomedical and Health Sciences
Hiroshima University
AY2019

Chief academic supervisor: Professor Kotaro Tanimoto
（Department of Orthodontics and Craniofacial Developmental Biology）

Abstract
Recently, we identified an expected role of matrix vesicles (MVs), budding from
osteoblasts, in delivery of microRNAs to bone matrix. Of these, miR-125b inhibits
osteoclast formation by targeting Prdm1, a transcriptional repressor of antiosteoclastogenesis factors. Transgenic (Tg) mice overexpressing miR-125b in
osteoblasts grow normally but exhibit high trabecular bone mass. We then determined
whether miR-125b overexpression in osteoblasts affects bone development, aging, and
fracture healing in mice. There were no significant differences in primary ossification
center and lateral (periosteal) bone formation and mineral apposition rate between Tg
and wild type (WT) mice during early bone development (from embryonic day 16.5).
However, medial (endosteal) bone resorption and osteoclast number were less in Tg
than WT mice, in parallel with increased trabecular bone mass. When compared with
WT mice, Tg mice retained bone mass, phosphate/amide I ratio and mechanical strength
even at 77 weeks old. During fracture healing, callus formation progressed equally in
Tg and WT mice, while callus resorption was delayed in Tg mice with decreased
number of osteoclasts. Taken together, our data suggest that miR-125b overexpression

in osteoblasts may increase bone mass and strength with decreased number of
osteoclasts while keeping bone formation and bone quality. These findings may provide
a novel therapeutic target for bone loss.