DEVLIN, M.J.*; LIEBERMAN, D.E.; OLSEN, B.R.; FUKAI, N.; Harvard University; Harvard University; Harvard Medical School; Harvard Medical School: The role of estradiol in mechanotransduction
Despite evidence that mechanical loads can induce diaphyseal bone growth, the mechanisms of mechanotransduction in growing bone are poorly understood. One hypothesis is that hormone levels affect osteoblast response to mechanical stimuli. While many hormones may be involved, this study focuses on estradiol (E2). Recent studies suggest that mechanotransduction in osteoblasts involves activation of estrogen receptor alpha (ER-α). Because E2 levels affect expression of ER-α, variation in E2 is predicted to affect osteogenic responses to loading by affecting receptor density. This hypothesis was tested in periosteal bone in two experiments.
First, 16 lambs (Ovis aries) were divided into low and high E2 treatment groups. The low-E2 group was immunized against GnRH; the high-E2 group received E2 capsules. Half of each group was sedentary, and half exercised for 40 min/day for 45 days. Fluorochrome dyes labeled bone growth. Results indicate that in the femur, mean daily apposition rate (DAR) in exercised animals is 44% higher in high-E2 than in low-E2 animals (p<.05), and 26% higher than in sedentary, high-E2 animals (p<.05). In the tibia, mean DAR in exercised animals is 42% higher in high-E2 than in low-E2 animals (p<.09), and 66% higher than in sedentary, high-E2 animals (p<.05). In the metatarsal, mean DAR in exercised animals is 75% higher in high-E2 than in low-E2 animals (p<.03), and 75% higher than in sedentary, high-E2 animals (p<.03).
Second, 36 ovariectomized C57BL/6J mice were divided into normal, high, and low E2 treatment groups implanted with 0.25 mg, 2.5 mg, or placebo E2 pellets. Half of the mice in each E2 group were fed normal mouse pellets, while half were fed the same pellets after they had been powdered and moistened. Results indicate that in the lateral mandibular corpus, hard diet animals exhibit 260% (high E2), 21% (low E2), and 82% (placebo) more growth than soft diet animals (p=.01 to 0.03). In situ hybridization shows that ER-α expression rises with increasing E2 doses. These studies support the hypothesis that variation in E2 level affects diaphyseal bone growth via regulation of ER-α.
