Dramatic decrease of innervation density in bone after ovariectomy

B Burt-Pichat, M H Lafage-Proust, F Duboeuf, N Laroche, Cecile Itzstein, L Vico, P D Delmas, C Chenu

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Abstract

Recent studies have demonstrated that bone is highly innervated and contains neuromediators that have functional receptors on bone cells. However, no data exist concerning the quantitative changes of innervation during bone loss associated with estrogen withdrawal. To study the involvement of nerve fibers in the regulation of bone remodeling, we have evaluated the modifications of innervation in a classical in vivo model of osteopenia in rats, ovariectomy (OVX). Skeletal innervation was studied by immunocytochemistry using antibodies directed against specific neuronal markers, neurofilament 200 and synaptophysin, and the neuromediator glutamate. Sciatic neurectomy, another model of bone loss due to limb denervation and paralysis, was used to validate our quantitative image analysis technique of immunostaining for nerve markers. Female Wistar rats at 12 wk of age were sham-operated (SHAM) or ovariectomized (OVX). Bone mineral density measurement and bone histomorphometry analysis of tibiae 14 d after surgery demonstrated a significant bone loss in OVX compared with SHAM. We observed an important reduction of nerve profile density in tibiae of OVX animals compared with SHAM animals, whereas innervation density in skin and muscles was similar for OVX and control rats. Quantitative image analysis of immunostainings demonstrated a significant decrease of the percentage of immunolabeling per total bone volume of neurofilament 200, synaptophysin, and glutamate in both the primary and secondary spongiosa of OVX rats compared with SHAM. These data indicate for the first time that OVX-induced bone loss in rat tibiae is associated with a reduction in nerve profile density, suggesting a functional link between the nervous system and the bone loss after ovariectomy.
Original languageEnglish
Pages (from-to)503-510
Number of pages8
JournalEndocrinology
Volume146
Issue number1
DOIs
Publication statusPublished - Jan 2004

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Ovariectomy
Bone Density
Bone and Bones
Tibia
Synaptophysin
Glutamic Acid
Bone Remodeling
Metabolic Bone Diseases
Denervation
Nerve Fibers
Paralysis
Nervous System
Wistar Rats
Estrogens
Extremities
Immunohistochemistry
Muscles
Skin
salicylhydroxamic acid
Antibodies

Keywords

  • animals
  • bone density
  • female
  • hind limb
  • male
  • skeletal muscle
  • nervous system
  • ovariectomy
  • postoperative period
  • rats
  • Wistar rats
  • skin
  • tibia
  • estrogen receptor alpha
  • sympathetic nervous system
  • NMDA glutamate receptors
  • messenger RNA
  • immunoreactive nerves
  • cancellous bone
  • mineral density
  • rat osteoblasts
  • spinal cord
  • beta

Cite this

Burt-Pichat, B., Lafage-Proust, M. H., Duboeuf, F., Laroche, N., Itzstein, C., Vico, L., ... Chenu, C. (2004). Dramatic decrease of innervation density in bone after ovariectomy. Endocrinology, 146(1), 503-510. https://doi.org/10.1210/en.2004-0884

Dramatic decrease of innervation density in bone after ovariectomy. / Burt-Pichat, B; Lafage-Proust, M H; Duboeuf, F; Laroche, N; Itzstein, Cecile; Vico, L; Delmas, P D; Chenu, C.

In: Endocrinology, Vol. 146, No. 1, 01.2004, p. 503-510.

Research output: Contribution to journalArticle

Burt-Pichat, B, Lafage-Proust, MH, Duboeuf, F, Laroche, N, Itzstein, C, Vico, L, Delmas, PD & Chenu, C 2004, 'Dramatic decrease of innervation density in bone after ovariectomy', Endocrinology, vol. 146, no. 1, pp. 503-510. https://doi.org/10.1210/en.2004-0884
Burt-Pichat B, Lafage-Proust MH, Duboeuf F, Laroche N, Itzstein C, Vico L et al. Dramatic decrease of innervation density in bone after ovariectomy. Endocrinology. 2004 Jan;146(1):503-510. https://doi.org/10.1210/en.2004-0884
Burt-Pichat, B ; Lafage-Proust, M H ; Duboeuf, F ; Laroche, N ; Itzstein, Cecile ; Vico, L ; Delmas, P D ; Chenu, C. / Dramatic decrease of innervation density in bone after ovariectomy. In: Endocrinology. 2004 ; Vol. 146, No. 1. pp. 503-510.
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AB - Recent studies have demonstrated that bone is highly innervated and contains neuromediators that have functional receptors on bone cells. However, no data exist concerning the quantitative changes of innervation during bone loss associated with estrogen withdrawal. To study the involvement of nerve fibers in the regulation of bone remodeling, we have evaluated the modifications of innervation in a classical in vivo model of osteopenia in rats, ovariectomy (OVX). Skeletal innervation was studied by immunocytochemistry using antibodies directed against specific neuronal markers, neurofilament 200 and synaptophysin, and the neuromediator glutamate. Sciatic neurectomy, another model of bone loss due to limb denervation and paralysis, was used to validate our quantitative image analysis technique of immunostaining for nerve markers. Female Wistar rats at 12 wk of age were sham-operated (SHAM) or ovariectomized (OVX). Bone mineral density measurement and bone histomorphometry analysis of tibiae 14 d after surgery demonstrated a significant bone loss in OVX compared with SHAM. We observed an important reduction of nerve profile density in tibiae of OVX animals compared with SHAM animals, whereas innervation density in skin and muscles was similar for OVX and control rats. Quantitative image analysis of immunostainings demonstrated a significant decrease of the percentage of immunolabeling per total bone volume of neurofilament 200, synaptophysin, and glutamate in both the primary and secondary spongiosa of OVX rats compared with SHAM. These data indicate for the first time that OVX-induced bone loss in rat tibiae is associated with a reduction in nerve profile density, suggesting a functional link between the nervous system and the bone loss after ovariectomy.

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