Nucleus pulposus (NP) degeneration is the major cause of degenerative disc disease (DDD). This condition cannot be treated or attenuated by traditional open or minimally invasive surgical options. However, a combination of stem cells, growth factors (GFs) and biomaterials present a viable option for regeneration. Injectable biomaterials act as carriers for controlled release of GFs and deliver stem cells to target tissues through a minimally invasive approach. In this study, injectable gelatin methacryloyl microspheres (GMs) with controllable, uniform particle sizes were rapidly biosynthesized through a low-cost electrospraying method. The GMs were used as delivery vehicles for cells and GFs, and they exhibited good mechanical properties and biocompatibility and enhanced the in vitro differentiation of laden cells into NP-like phenotypes. Furthermore, this integrated system attenuated the in vivo degeneration of rat intervertebral discs, maintained NP tissue integrity and accelerated the synthesis of extracellular matrix. Therefore, this novel therapeutic system is a promising option for the treatment of DDD.
Inflammation and neuronal apoptosis aggravate the secondary damage after spinal cord injury (SCI). Rehmannioside A (Rea) is a bioactive herbal extract isolated from
Rehmanniae radix
with low toxicity and neuroprotection effects. Rea treatment inhibited the release of pro‐inflammatory mediators from microglial cells, and promoted M2 polarization in vitro, which in turn protected the co‐cultured neurons from apoptosis via suppression of the NF‐κB and MAPK signalling pathways. Furthermore, daily intraperitoneal injections of 80 mg/kg Rea into a rat model of SCI significantly improved the behavioural and histological indices, promoted M2 microglial polarization, alleviated neuronal apoptosis, and increased motor function recovery. Therefore, Rea is a promising therapeutic option for SCI and should be clinically explored.
Over‐activated osteoclastogenesis, which is initiated by inflammation, has been implicated in osteoporosis. Corilagin, a natural compound extracted from various medicinal herbaceous plants, such as Cinnamomum cassia, has antioxidant and anti‐inflammatory activities. We found that Corilagin suppressed osteoclast differentiation in a dose‐dependent manner, significantly decreased osteoclast‐related gene expression and impaired bone resorption by osteoclasts. Moreover, phosphorylation of members of the nuclear factor‐kappaB (NF‐κB) and PI3K/AKT signalling pathways was reduced by Corilagin. In a murine model of osteoporosis, Corilagin inhibited osteoclast functions in vivo and restored oestrogen deficiency‐induced bone loss. In conclusion, our findings suggested that Corilagin inhibited osteoclastogenesis by down‐regulating the NF‐κB and PI3K/AKT signalling pathways, thus showing its potential possibility for the treatment of osteoporosis.
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Transmembrane integrin receptors represent a major composition of cell- extracellular matrix (ECM)
communications that mediate cellular biological activities including proliferation and differentiation. Stem cells, especially
mesenchymal stem cells (MSC) have rapidly emerged as promising therapies for various diseases. Dynamic links exist
between extracellular and intracellular environments that profoundly influence the cellular activities via integrin receptors,
such as cell morphology transformation and differentiation. Interpreting the roles of integrin receptors in the regulation of
MSC differentiation may potentially lead to amplified therapeutic effect. In this review, we summarize, for the first time,
the potential mechanisms by which integrins promote MSC multilineage differentiation including integrin downstream
signaling cascades and the interactions between integrin and ion channels, the cytoskeleton and nuclear mechanoresponses.
Furthermore, we focus on the current state and future prospects of the application of integrins to promote cell differentiation.
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