Table 1 Effects of neuro-associated molecules on bone regeneration

Neurotransmitters

NE

α-AR; β-AR

MC3T3-E1 cell line

α₁B^−/− mice

Promote Cebpd gene expression and cell proliferation;

Increase bone formation

Tanaka et al. [54]

ACh

nAChRs; mAChRs

Mouse osteoblasts

α₂nAChR^−/− mice

Regulate osteoblast proliferation;

Enhance osteoclast apoptosis;

Inhibit mineralized matrix resorption

Bajayo et al. [55]

Neuropeptides

CGRP

CRLR; RAMP1

Mouse osteoclast precursor cells;

Mouse osteoblasts

A femoral fracture model in αCGRP^−/− mice

Promote osteogenic differentiation and adequate callus formation

Appelt et al. [56]

SP

NK-1R

Rat MSCs

A femoral defect model in SD rats

Promote MSC recruitment and efficient osseointegration

Mu et al. [57]

NPY

Y1R; Y2R

Mouse BMSCs

A femoral defect in NPY^−/− mice

Decrease cancellous bone volume;

Inhibit bone formation rate

Baldock et al. [58]

Axon guidance factors

Sema3A

Neuropilin-1 & plexin-A

–

A calvarial defect model in SD rats

Inhibit RANKL expression;

Increase callus and bone formation

Kenan et al. [59]

Sema4D

Plexin-B1; plexin-B2

Mouse calvarial cells;

Wild-type and Sema4d^−/− osteoclasts;

Wild-type and Plxnb1^−/− osteoblasts

An OVX model in mice, Sema4d^−/− mice; and Plxnb1^−/− mice

Inhibit osteoblast differentiation by RhoA activation;

Reduce bone formation

Negishi-Koga et al. [60]

SLIT3

ROBO1

Mouse calvaria cells;

Human BMSCs;

MC3T3-E1 cell line;

Mouse BMMs;

RAW264.7 cells

An OVX model in mice, Slit3^−/− mice; and Robo1^−/− mice

Stimulate osteoblast migration and proliferation;

Regulate bone remodeling

Kim et al. [61]

Neurotrophins

NGF

TrkA; p75NTR

–

A tibial fracture model in mice

Accelerate the conversion of cartilage to bone;

Result in highly connected trabecular bone

Rivera et al. [62]

BDNF

TrkB

MC3T3-E1 cell line; ST-2 mouse bone marrow stromal cells

An OVX model in SD rats

Promote osteoblast differentiation and mineralization;

Reduce osteoclast formation in vivo

Park et al. [63]

NT3

TrkC

MC3T3-E1 cell line

A proximal tibial defect in SD rats

Suppress chondrogenesis;

Enhance osteogenesis and angiogenesis

Su et al. [64]