Mechanical loading differentially affects osteocytes in fibulae from lactating mice compared to osteocytes in virgin mice: Possible role for lacuna size

H. Hemmatian, R. Jalali, C.M. Semeins, J.M.A. Hogervorst, G.H. van Lenthe, J. Klein-Nulend, A.D. Bakker

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)675-685
JournalCalcified Tissue International
Volume103
Issue number6
Early online date14 Aug 2018
DOIs
Publication statusPublished - Dec 2018

Bibliographical note

With supplementary files

Funding

The authors thank Marion A. van Duin and Hans Korfage for their expert technical support. We would like to thank Rishikesh N. Kulkarni for his help in performing the validation experiments. We thank Nynke Mostard and Janneke D. van Capelle for their help in validating and scoring of the sclerostin staining. H. Hemmatian, R. Jalali, C. M. Semeins, J. M. A. Hogervorst, G. H. van Lenthe, J. Klein-Nulend, and A. D. Bakker, declare that they have no conflict of interests. Funding This research was funded by the European Commission through MOVE-AGE, an Erasmus Mundus Joint Doctorate programme (2011-0015).

FundersFunder number
Marion A. van Duin
European Commission2011-0015

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