Roles of neurotrophins in skeletal tissue formation and healing

Abstract

Neurotrophins and their receptors are key molecules that are known to be critical in regulating nervous system development and maintenance and have been recognized to be also involved in regulating tissue formation and healing in skeletal tissues. Studies have shown that neurotrophins and their receptors are widely expressed in skeletal tissues, implicated in chondrogenesis, osteoblastogenesis, and osteoclastogenesis, and are also involved in regulating tissue formation and healing events in skeletal tissue. Increased mRNA expression for neurotrophins NGF, BDNF, NT-3, and NT-4, and their Trk receptors has been observed in injured bone tissues, and NT-3 and its receptor, TrkC, have been identified to have the highest induction at the injury site in a drill-hole injury repair model in both bone and the growth plate. In addition, NT-3 has also recently been shown to be both an osteogenic and angiogenic factor, and this neurotrophin can also enhance expression of the key osteogenic factor, BMP-2, as well as the major angiogenic factor, VEGF, to promote bone formation, vascularization, and healing of the injury site. Further studies, however, are needed to investigate if different neurotrophins have differential roles in skeletal repair, and if NT-3 can be a potential target of intervention for promoting bone fracture healing.

Neonatal systemic inflammation and the risk of low scores on measures of reading and mathematics achievement at age 10 years among children born extremely preterm

“…According to this hypothesis the mother and/or placenta provide the fetus with proteins needed for brain maturation, and birth before the newborn can synthesize adequate amounts of these proteins deprives the brain of needed brain‐maturation enhancers (Reuss et al, 1994). These proteins with neurotrophic properties, which are often growth factors, are now recognized as having angiogenic properties (Su et al, 2018; Kermani et al, 2005; Usui et al, 2014), and capable of reducing the risk of brain damage and/or promoting repair (Larpthaveesarp et al, 2015; Wagenaar et al, 2017) Some of these proteins are viewed as mainly neurotrophic, while others are primarily considered angiogenic (Jin et al, 2002; Sun et al, 2003). Regardless, these proteins almost invariably have both neurotrophic and angiogenic properties (Sun et al, 2003; Madri, 2009; Meng et al, 2014; Rosa et al, 2010; Marteau et al, 2011; Liu et al, 2009; Wang et al, 2015; Hansen et al, 2008; Kosacka et al, 2006).…”

The expressions of NGF and VEGF in the fracture tissues are closely associated with accelerated clavicle fracture healing in patients with traumatic brain injury

“… 27 Beside its expression in bone marrow mesenchymal stromal cells (MSCs), NGF expression was also detected in osteogenic cells, periosteal mesenchymal osteoprogenitor cells, superficial osteocytes, and osteoblastic progenitor cells and upregulated during the proliferation phase. 28 VEGF expression is not limited in endothelial cells and is also detected in various nonvascular cells, such as type 2 pneumocytes, monocytes, megakaryocytes, dendritic cells, hematopoietic stem cells, lens epithelial cells, and a variety of neural cells. 29 Hypoxia is one of the most important stimuli of VEGF expression and beneficial for fracture healing.…”

Recent Advancements in Gene and Stem Cell‐Based Treatment Modalities: Potential Implications in Noise‐Induced Hearing Loss

“…NTs are a family of proteins that induce neuronal growth and differentiation by interacting with two cell‐surface receptors, namely Trk tyrosine kinase and p75 receptor (Nittoli et al, ; Su et al, ). While NT's role in neurodegenerative diseases has already begun to be recognized, the same concept can be applied to hearing loss.…”