Senescence of endplate osteoclasts induces sensory innervation and spinal pain

  1. Dayu Pan
  2. Kheiria Gamal Benkato
  3. Xuequan Han
  4. Jinjian Zheng
  5. Vijay Kumar
  6. Mei Wan
  7. Junying Zheng
  8. Xu Cao  Is a corresponding author
  1. Department of Orthopedic Surgery and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, United States
15 figures and 1 additional file

Figures

Figure 1 with 1 supplement
A greater number of senescent osteoclasts (SnOCs) are associated with endplate degeneration and spinal hypersensitivity in the lumbar spine instability (LSI) and aged mouse models.

(a–c) Spontaneous activity, including active time (a), distance traveled (b), and maximum speed (c) on the wheel within 48 hr in the sham, LSI injury, and aged mice. (d) Time in seconds spent on a …

Figure 1—figure supplement 1
Increased occurrence of SnOCs in the endplates of two LBP models compared to the control young sham mice.

(a) Representative images of immunofluorescent analysis of HMGB1, a senescent marker (green), tartrate-resistant acid phosphatase positive (TRAP), an osteoclast marker (red) and nuclei …

ABT263 effectively depletes endplate senescent osteoclasts (SnOCs) in the lumbar spine instability (LSI) and aging mouse models.

(a–c) Immunofluorescent staining of p16 (green), tartrate-resistant acid phosphatase (TRAP) (red), and nuclei (4′,6-diamidino-2-phenylindole [DAPI]; blue) of the endplates in aged (a) and LSI mice (b

ABT263 treatment improves the symptomatic spinal pain behavior in the aged and lumbar spine instability (LSI) mouse models.

(a, b) The paw withdrawal frequency (PWF) in response to mechanical stimulation (von Frey test, 0. 07 g (a) and 0.4 g (b)) in aged mice treated with PBS or ABT263 compared to young adult mice. (c–e) …

Depletion of senescent osteoclasts (SnOCs) reduces spinal degeneration and sustains endplate microarchitecture in aged mice.

(a) Microcomputed tomography (μCT) images of the aged mouse caudal endplates of L4–L5 injected with PBS or ABT263. Scale bar, 1 mm. (b) Representative images of Safranin O and fast green staining of …

Depletion of senescent osteoclasts (SnOCs) reduces spinal degeneration and sustains endplate microarchitecture in lumbar spine instability (LSI) mice.

(a) Microcomputed tomography (μCT) images of adult sham mice and 3-month-old LSI model mice caudal endplates of L4–L5 injected with PBS or ABT263. Scale bar, 1 mm. (b) Representative images of …

Figure 6 with 1 supplement
Depletion of senescent osteoclasts (SnOCs) abrogates sensory innervation and pain in aged and lumbar spine instability (LSI) mouse models.

(a) Representative images of immunofluorescent analysis of calcitonin gene-related peptide (CGRP) (green), PGP9.5 (red), and nuclei (4′,6-diamidino-2-phenylindole [DAPI]; blue) of adult sham, LSI, …

Figure 6—figure supplement 1
ELISA analysis of Netrin-1 and NGF in L3–5 endplates of sham, LSI+PBS, and LSI+ABT263 mice.

(a) Enzyme-linked immunosorbent assay (ELISA) analysis showing the concentration of Netrin-1 in L3–5 endplates of adult sham, lumbar spine instability (LSI) + PBS, and LSI + ABT263 mice. (b) ELISA …

Depletion of senescent osteoclasts (SnOCs) abrogates blood vessels innervation in aged and lumbar spine instability (LSI) mouse models.

(a) Representative images of immunofluorescent analysis of CD31, an angiogenesis marker (green), Emcn, an endothelial cell marker (red) and nuclei (4′,6-diamidino-2-phenylindole [DAPI]; blue) of …

Schematic diagram of senescent osteoclasts (SnOCs) in porous endplate-induced spinal pain.

In lumbar spine instability (LSI) or aging mouse models there is an induction of spinal hypersensitivity due to increased numbers of SnOCs in the endplate, leading to excessive secretion of sensory …

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