Bone tissue is densely innervated, and there is increasing evidence for a neural control of bone metabolism. Semaphorin-3A is a very important regulator of neuronal targeting in the peripheral nervous system as well as in angiogenesis, and knockout of the Semaphorin-3A gene induces abnormal bone and cartilage development. We analyzed the spatial and temporal expression patterns of Semaphorin-3A signaling molecules during endochondral ossification, in parallel with the establishment of innervation. We show that osteoblasts and chondrocytes differentiated in vitro express most members of the Semaphorin-3A signaling system (Semaphorin-3A, Neuropilin-1, and Plexins-A1 and -A2). In vitro, osteoclasts express most receptor chains but not the ligand. In situ, these molecules are all expressed in the periosteum and by resting, prehypertrophic and hypertrophic chondrocytes in ossification centers before the onset of neurovascular invasion. They are detected later in osteoblasts and also osteoclasts, with differences in intensity and regional distribution. Semaphorin-3A and Neuropilin-1 are also expressed in the bone marrow. Plexin-A3 is not expressed by bone cell lineages in vitro. It is detected early in the periosteum and hypertrophic chondrocytes. After the onset of ossification, this chain is restricted to a network of cell processes in close vicinity to the cells lining the trabeculae, similar to the pattern observed for neural markers at the same stages. After birth, while the density of innervation decreases, Plexin-A3 is strongly expressed by blood vessels on the ossification front. In conclusion, Semaphorin-3A signaling is present in bone and seems to precede or coincide at the temporal but also spatial level with the invasion of bone by blood vessels and nerve fibers. Expression patterns suggest Plexin-A3/Neuropilin-1 as a candidate receptor in target cells for the regulation of bone innervation by Semaphorin-3A.

Download full-text PDF

Source
http://dx.doi.org/10.1002/dvdy.20512DOI Listing

Publication Analysis

Top Keywords

semaphorin-3a signaling
12
endochondral ossification
8
bone
8
semaphorin-3a
8
expression patterns
8
semaphorin-3a neuropilin-1
8
hypertrophic chondrocytes
8
expressed bone
8
plexin-a3 expressed
8
blood vessels
8

Similar Publications

Objectives: The osteogenic potential of periodontal ligament stem cells (PDLSCs) is crucial for periodontal tissue regeneration. Prolonged and excessive oxidative stress (OS) impairs the osteogenic function of PDLSCs. Recently, Semaphorin 3A (Sema3A) has been reported to have multiple roles in bone protection.

View Article and Find Full Text PDF
Article Synopsis
  • Recent research indicates that blocking the RIPK1/RIPK3/MLKL necrosome can help reduce inflammatory pain linked to conditions like demyelination in the central nervous system.
  • This study tests necrostatin-1s (Nec-1s), a specific RIPK1 inhibitor, on LPS-induced inflammatory pain in male mice, assessing pain sensitivity through hot plate tests and examining related protein changes.
  • Results show that Nec-1s not only prevents LPS-induced pain relief but also reverses the activation of key proteins and signals involved in inflammation and demyelination, suggesting that RIPK1 inhibitors could be a promising treatment for managing inflammatory pain.
View Article and Find Full Text PDF

[Semaphorin-3A signaling decreases the porosity of sinusoidal endothelial cells in steatotic liver diseases].

Med Sci (Paris)

November 2024

Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR1149, Paris, France - APHP, Hôpital européen George Pompidou, Hôpital Corentin-Celton, Service de gériatrie, Institut CARPEM, Paris, France.

View Article and Find Full Text PDF

The ataxia-telangiectasia disease protein ATM controls vesicular protein secretion via CHGA and microtubule dynamics via CRMP5.

Neurobiol Dis

December 2024

Goethe University Frankfurt, University Hospital, Clinic of Neurology, Exp. Neurology, Heinrich Hoffmann Str. 7, 60590 Frankfurt am Main, Germany. Electronic address:

The autosomal recessive disease ataxia-telangiectasia (A-T) presents with cerebellar degeneration, immunodeficiency, radiosensitivity, capillary dilatations, and pulmonary infections. Most symptoms outside the nervous system can be explained by failures of the disease protein ATM as a Ser/Thr-kinase to coordinate DNA damage repair. However, ATM in adult neurons has cytoplasmic localization and vesicle association, where its roles remain unclear.

View Article and Find Full Text PDF
Article Synopsis
  • * Retinal ganglion cells (RGCs) are neurons that respond to optic nerve injuries by activating processes that can lead to cell death, while microglia, which indicate inflammation, become activated after injury.
  • * In a study using a mouse model, it was found that inhibiting the phosphorylation of the protein CRMP2 reduced RGC loss and microglial activation, suggesting potential treatments for optic nerve injuries and related neurodegenerative diseases.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!