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Calcified Tissue International

, Volume 105, Issue 3, pp 316–330 | Cite as

Increased Cellular Presence After Sciatic Neurectomy Improves the Bone Mechano-adaptive Response in Aged Mice

  • Judith Piet
  • Dorothy Hu
  • Quentin Meslier
  • Roland Baron
  • Sandra J. ShefelbineEmail author
Original Research

Abstract

The mechano-adaptive response of bone to loading in the murine uniaxial tibial loading model is impaired in aged animals. Previous studies have shown that in aged mice, the amount of bone formed in response to loading is augmented when loads are applied following sciatic neurectomy. The synergistic effect of neurectomy and loading remains to be elucidated. We hypothesize that sciatic neurectomy increases cellular presence, thereby augmenting the response to load in aged mice. We examined bone adaptation in four groups of female C57BL/6J mice, 20–22 months old: (1) sham surgery + 9N loading; (2) sciatic neurectomy, sacrificed after 5 days; (3) sciatic neurectomy, sacrificed after 19 days; (4) sciatic neurectomy + 9N loading. We examined changes in bone cross sectional properties with micro-CT images, and static and dynamic histomorphometry with histological sections taken at the midpoint between tibiofibular junctions. The response to loading at 9N was not detectable with quantitative micro-CT data, but surface-specific histomorphometry captured an increase in bone formation in specific regions. 5 days following sciatic neurectomy, the amount of bone in the neurectomized leg was the same as the contralateral leg, but 19 days following sciatic neurectomy, there was significant bone loss in the neurectomized leg, and both osteoclasts and osteoblasts were recruited to the endosteal surfaces. When sciatic neurectomy and loading at 9N were combined, 3 out of 4 bone quadrants had increased bone formation, on the endosteal and periosteal surfaces (increased osteoid surface and mineralizing surface respectively). These data demonstrate that sciatic neurectomy increases cellular presence on the endosteal surface. With long-term sciatic-neurectomy, both osteoclasts and osteoblasts were recruited to the endosteal surface, which resulted in increased bone formation when combined with a sufficient mechanical stimulus. Controlled and localized recruitment of both osteoblasts and osteoclasts combined with appropriate mechanical loading could inform therapies for mechanically-directed bone formation.

Keywords

Mechano-adaptation Bone Sciatic neurectomy Tibial loading 

Notes

Funding

This work received internal funding from Northeastern University.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and Animal Rights

All animal procedures received approval from Northeastern University’s Institutional Animal Care and Use Committee (IACUC).

Supplementary material

223_2019_572_MOESM1_ESM.docx (491 kb)
Supplementary material 1 (DOCX 490 kb)
223_2019_572_MOESM2_ESM.xlsx (34 kb)
Supplementary material 2 (XLSX 34 kb)

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Authors and Affiliations

  1. 1.Department of BioengineeringNortheastern UniversityBostonUSA
  2. 2.Department of Mechanical and Industrial EngineeringNortheastern UniversityBostonUSA
  3. 3.Department of MedicineHarvard Medical SchoolBostonUSA
  4. 4.Division of Bone and Mineral Research, Department of Oral Medicine, Infection and ImmunityHarvard School of Dental MedicineBostonUSA

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