Injectable Nanocomposite Hydrogels for Intervertebral Disc Degeneration: Combating Oxidative Stress, Mitochondrial Dysfunction, and Ferroptosis.

Intervertebral disc degeneration (IVDD) is a major cause of low back pain, where oxidative stress and mitochondrial dysfunction are key contributors. Additionally, ferroptosis, an iron-dependent form of cell death, is identified as a critical mechanism in IVDD pathogenesis. Herein, the therapeutic potential of gallic acid (GA)-derived PGA-Cu nanoparticles, enhanced with functional octapeptide (Cys-Lys-His-Gly-d-Arg-d-Tyr-Lys-Phe, SS08) to build the mitochondria-targeted nanoparticles (PGA-Cu@SS08), and embedded within a hydrogel matrix to form a nanocomposite hydrogel, is explored.

TET enzymes regulate skeletal development through increasing chromatin accessibility of RUNX2 target genes.

The Ten-eleven translocation (TET) family of dioxygenases mediate cytosine demethylation by catalyzing the oxidation of 5-methylcytosine (5mC). TET-mediated DNA demethylation controls the proper differentiation of embryonic stem cells and TET members display functional redundancy during early gastrulation. However, it is unclear if TET proteins have functional significance in mammalian skeletal development.

Mechanical regulation of bone remodeling.

Bone remodeling is a lifelong process that gives rise to a mature, dynamic bone structure via a balance between bone formation by osteoblasts and resorption by osteoclasts. These opposite processes allow the accommodation of bones to dynamic mechanical forces, altering bone mass in response to changing conditions. Mechanical forces are indispensable for bone homeostasis; skeletal formation, resorption, and adaptation are dependent on mechanical signals, and loss of mechanical stimulation can therefore significantly weaken the bone structure, causing disuse osteoporosis and increasing the risk of fracture.

Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk.

Wolff's law and the Utah Paradigm of skeletal physiology state that bone architecture adapts to mechanical loads. These models predict the existence of a mechanostat that links strain induced by mechanical forces to skeletal remodeling. However, how the mechanostat influences bone remodeling remains elusive.

Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts.

The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes, and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis.

Immune response of interferon-γ-inducible lysosomal thiol reductase (GILT) from Chinese sturgeon (Acipenser sinensis) to microbial invasion and its antioxdative activity in lipopolysaccharides-treated mammalian dentritic cells.

Interferon-γ-inducible lysosomal thiol reductase (GILT) plays an important role in the major histocompatibility complex-restricted antigen processing of endocytosed proteins via catalyzing the disulfide bond reduction in the endocytic pathway. Here, the cDNA of Chinese sturgeon (Acipenser sinensis) GILT (CsGILT) was cloned. It contained an open reading frame of 762 nucleotides encoding a protein of 254 amino acids with an estimated molecular weight of 28.

MHC class II alpha, beta and MHC class II-associated invariant chains from Chinese sturgeon (Acipenser sinensis) and their response to immune stimulation.

The major histocompatibility complex class II (MHC II) molecules play a vital role in adaptive immune response through presenting antigenic peptides to CD4 T lymphocytes. To accomplish this physiologic function, the MHC class II-associated invariant chain interacts with the MHC II α/β subunits and promotes their correct assembly and efficient traffic. Here, we isolated the cDNAs of MHC II α, β and MHC II-associated invariant chains (designated as CsMHC II α, CsMHC II β, and CsMHC II γ) from Chinese sturgeon (Acipenser sinensis).

Three ferritin subunit analogs in Chinese giant salamander (Andrias davidianus) and their response to microbial stimulation.

Ferritin, an evolutionarily conserved iron-binding protein, plays important roles in iron storage and detoxification and in host immune response to invading stimulus as well. In the present study, we identified three ferritin subunit analog cDNAs from Chinese giant salamander (Andrias davidianus). All the three ferritin subunit cDNAs had a putative iron responsive element in the 5'-untranslated region.