Abstract
Hormonal changes during lactation are associated with profound changes in bone cell biology, such as osteocytic osteolysis, resulting in larger lacunae. Larger lacuna shape theoretically enhances the transmission of mechanical signals to osteocytes. We aimed to provide experimental evidence supporting this theory by comparing the mechanoresponse of osteocytes in the bone of lactating mice, which have enlarged lacunae due to osteocytic osteolysis, with the response of osteocytes in bone from age-matched virgin mice. The osteocyte mechanoresponse was measured in excised fibulae that were cultured in hormone-free medium for 24 h and cyclically loaded for 10 min (sinusoidal compressive load, 3000 µε, 5 Hz) by quantifying loading-related changes in Sost mRNA expression (qPCR) and sclerostin and β-catenin protein expression (immunohistochemistry). Loading decreased Sost expression by ~ threefold in fibulae of lactating mice. The loading-induced decrease in sclerostin protein expression by osteocytes was larger in lactating mice (55% decrease ± 14 (± SD), n = 8) than virgin mice (33% decrease ± 15, n = 7). Mechanical loading upregulated β-catenin expression in osteocytes in lactating mice by 3.5-fold (± 0.2, n = 6) which is significantly (p < 0.01) higher than the 1.6-fold increase in β-catenin expression by osteocytes in fibulae from virgin mice (± 0.12, n = 4). These results suggest that osteocytes in fibulae from lactating mice with large lacunae may respond stronger to mechanical loading than those from virgin mice. This could indicate that osteocytes residing in larger lacuna show a stronger response to mechanical loading.
Highlights
Lactation is associated with large shifts in hormonal status
The fibulae of lactating and virgin mice were selected to investigate the effect of lacuna shape on the responses of osteocytes to the mechanical loading
We aimed to quantify the response of osteocytes in mechanically loaded fibulae from lactating and virgin mice of similar age, gender, and genetic background, having different lacunar morphology, as measured by quantifying protein expression of the established mechanoresponsive proteins sclerostin and β-catenin as well as sclerostin gene (Sost) gene expression
Summary
Lactation is associated with large shifts in hormonal status. PTHrP and prolactin go up, PTH and estrogen go down [1]. Evidence suggests that the osteocyte lacunae are becoming smaller and more spherical with aging [18, 19], while it has been shown that aging is associated with a reduced mechanoresponse [20,21,22], which suggest that altered lacunar shape is a possible cause of impaired loading-induced bone remodeling process in the elderly Up to this date, experimental evidence supporting, or refuting, the presupposition that changes in lacunar morphology as seen in lactation, aging, and disease, can underlie an altered bone responsiveness to mechanical loads is non-existent
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
