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In humans, the photoreceptor cells of the eye and sensory hair cells of the ear lack stem cells. These cells are thus unrenewable and cannot be replaced when they are damaged or destroyed.
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The somatosensory system relays sensory information from the skin, mucous membranes, limbs, and joints. Somatosensation is more familiarly known as the sense of touch. A typical somatosensory pathway includes three types of long neurons: primary, secondary, and tertiary. Primary neurons have cell bodies located near the spinal cord in groups of neurons called dorsal root ganglia. The sensory neurons of ganglia innervate designated areas of skin called dermatomes.
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Osteoblasts are inherently programmed to repel sensory innervation.

Luís Leitão1,2,3, Estrela Neto1,2, Francisco Conceição1,2,3

  • 11Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal.

Bone Research
|May 22, 2020
PubMed
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Osteoblasts, developing bone cells, create a signaling environment that repels sensory nerve growth by reducing nerve growth factors and increasing repulsive signals like Shh (Sonic hedgehog). This regulates sensory innervation in bone.

Keywords:
BoneHomeostasisNeurophysiology

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Area of Science:

  • Bone biology
  • Neuroscience
  • Cell signaling

Background:

  • Bone tissue is innervated by sensory neurons, crucial for skeletal development and function.
  • The mechanisms regulating sensory nerve mapping in bone remain poorly understood.
  • Mesenchymal stem cell differentiation into osteoblasts influences the bone microenvironment.

Purpose of the Study:

  • To investigate how osteoblast differentiation affects sensory innervation in bone.
  • To identify signaling molecules involved in the crosstalk between osteoblasts and sensory neurons.
  • To elucidate the role of osteoblast-derived signals in regulating sensory axon guidance.

Main Methods:

  • Co-culture of human mesenchymal stem cells and sensory neurons.
  • Analysis of gene and protein expression during osteoblast differentiation (NGF, BDNF, Sema3A, Wnt4, Shh).
  • Functional assays blocking Shh signaling to assess axonal repulsion.
  • In situ localization of Shh expression in bone tissue.

Main Results:

  • Osteoblast differentiation impairs axonal growth promotion and induces repulsion of sensory neurons.
  • Reduced expression of neurotrophic factors (NGF, BDNF) and increased expression of repulsive cues (Sema3A, Wnt4, Shh) occur during osteoblast differentiation.
  • Shh expression correlates with osteoblast differentiation stage and mediates axonal repulsion.
  • Blocking Shh signaling reverses the repulsive effect of osteoblasts on sensory axons.
  • Shh is expressed by osteoblasts in bone tissue.

Conclusions:

  • Osteoblast differentiation establishes a signaling milieu that actively shapes sensory innervation patterns in bone.
  • Osteoblast-derived Shh is a key regulator of sensory axon repulsion and patterning during bone development.
  • Understanding this crosstalk is vital for comprehending bone innervation and developing therapeutic strategies.