No Signature of Osteocytic Osteolysis in Cortical Bone from Lactating NMRI Mice
The roles of osteocytes in bone homeostasis have garnered increasing attention since it has been realized that osteocytes communicate with other organs. It has long been debated whether and/or to which degree osteocytes can break down the bone matrix surrounding them in a process called osteocytic osteolysis. Osteocytic osteolysis has been indicated to be induced by a number of skeletal challenges including lactation in CD1 and C57BL/6 mice, whereas immobilization-induced osteocytic osteolysis is still a matter of controversy. Motivated by the wish to understand this process better, we studied osteocyte lacunae in lactating NMRI mice, which is a widely used outbred mouse strain. Surprisingly, no trace of osteocytic osteolysis could be detected in tibial or femoral cortical bone either by 3D investigation by synchrotron nanotomography, by studies of lacunar cross-sectional areas using scanning electron microscopy, or by light microscopy. These results lead us to conclude that osteocytic osteolysis does not occur in NMRI mice as a response to lactation, in turn suggesting that osteocytic osteolysis may not play a generic role in mobilizing calcium during lactation.
KeywordsCortical bone Osteocyte Lacuno-canalicular network Osteocytic osteolysis Lactation Nanotomography
The authors are grateful for the excellent technical assistance of Jytte Utoft. We thank Visiopharm for the contribution to the newCAST stereology software system. The study was kindly supported by the A.P. Møller Foundation for Advancement of Medical Science, Health Aarhus University, the Novo Nordisk Foundation, Vanførefonden, Oda og Hans Svennings Fond, the VILLUM foundation (Grant 17553), and the Danish Agency for Science, Technology and Innovation (DANSCATT). Affiliation with the integrated materials research center (iMAT) at Aarhus University is gratefully acknowledged (HB, NKW). The synchrotron tomography experiments were performed on beamline ID16A at the European Synchrotron Radiation Facility (ESRF), Grenoble, France, through long-term proposal MD830. We are grateful to the beamline staff at the ESRF for providing assistance in using beamline ID16A.
Study design: HB, JST, FBG, AB, MHW. Synchrotron experiments: AP, MEB, NKW, FBG. SEM experiments: NKW, FBG. Optical microscopy: AB. Data analysis: NKW, HB, AB. Data interpretation: NKW, HB, AB. Drafting manuscript: NKW, HB. Revising manuscript content: NKW, HB, JST, AB, FBG. Approving the final version of manuscript: all authors. NKW and HB take responsibility for the integrity of the data analysis.
Compliance with Ethical Standards
Conflict of interest
Nina Kølln Wittig, Mie Elholm Birkbak, Fiona Linnea Bach-Gansmo, Alexandra Pacureanu, Mette Høegh Wendelboe, Annemarie Brüel, Jesper Skovhus Thomsen, and Henrik Birkedal declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
The study complied with the guiding principles in the European Communities Council Directive of 24 November 1986 (86/609/EEC) and was approved by the Danish Animal Experiments Inspectorate (2012-15-2934-00769).
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