CXCL9, also known as monokine induced by IFN-γ (MIG), is produced by myeloid cells in TME, and it mainly attracts CXCR3 receptor expressing cells, such as activated T cells and NK cells. More and more studies have found that CXCL9/10/11 plays an important role in the regulation of TME.
Growth and differentiation factor 8 (GDF-8), also known as myostatin, is a member of the transforming growth factor-β1 (TGF- β 1) superfamily of GDFs that is highly expressed in skeletal muscle. Myostatin binds the type IIB activin receptor (ActRIIB) and type I co-receptor (Alk4/5) to regulate the expression of downstream target genes such as myogenic differentiation protein (MyoD) and myogenic factor-5 (Myf-5) via a TGF-β signaling pathway.
NCAM is involved in cell-to-cell interactions as well as cell-matrix interactions during development and differentiation. It plays a role in the development of the nervous system by regulating neurogenesis, neurite outgrowth, and cell migration. It is also involved in the expansion of T lymphocytes, B lymphocytes and natural killer (NK) cells which play an important role in immune surveillance. It plays a role in signal transduction.
Neurofilament light chain (NfL) is an intermediate filament protein that constitutes intermediate filaments, a part of the cytoskeleton, of neurons (intermediate filaments are sometimes referred to as nanofilaments). Together with the other four neuronal intermediate filament proteins, namely neurofilament heavy chain, neurofilament medium chain, alpha-internexin and peripherin, NfL assembles into neurofilaments, which are important for dendritic branching and growth and stability of axons in both central and peripheral nerves and for post-traumatic axonal regeneration. Axonal damage leads to NfL release into the extracellular space.
Osteonectin was so named owing to its ability to bind to Ca2+, hydroxyapatite, and collagen and to nucleate hydroxyapatite deposition. Although osteonectin is highly enriched in bone, it is also expressed in a variety of other connective tissues at specific points during development, maturation, or repair processes in vivo. SPARC (secreted protein, acidic, rich in cysteine) was identified after induction by cAMP in teratocarcinoma cells and was found to be produced at very early stages of embryogenesis.
Osteopontin is the most abundant of the SIBLING proteins and is normally found in bone. Osteopontin made by stromal or inflammatory cells at sites of ectopic mineralization binds to mineral and physically inhibits crystal growth, leading to dissolution of the bioapatite. Osteopontin promotes regression of ectopic calcification and its expression is increased under conditions of injury and disease, including calcified deposits related to atherosclerotic lesions, aortic stenosis, kidney stones, and tumors.
Osteoprotegerin (OPG), a member of the TNF receptor family and expressed by osteoblasts, is now recognized for its action on the regulation of bone metabolism. It inhibits bone resorption by attaching with high affinity to its ligand RANKL, thus blocking the binding of RANKL with its receptor: RANK. This system is regulated by calciotropic hormones.
Periostin is a secreted extracellular matrix protein that functions in tissue development and regeneration, including wound healing, and ventricular remodeling following myocardial infarction. It binds to integrins to support adhesion and migration of epithelial cells. Periostin is involved in multiple steps of bone metabolism such as osteoblast differentiation, proliferation and adhesion; mediates bone repair and mechanical responses; and regulates bone remodelling and bone strength.
Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of plasminogen activators (PAs) and is therefore an important inhibitor of the plasminogen/plasmin system. Being the fast-acting inhibitor of tissue-type PA (tPA), PAI-1 primarily attenuates fibrinolysis. Through inhibition of urokinase-type PA (uPA) and interaction with biological ligands such as vitronectin and cell-surface receptors, the function of PAI-1 extends to pericellular proteolysis, tissue remodeling and other processes including cell migration.
Procollagen type III is found abundantly in skeletal muscle and other soft tissues such as skin, and in negligible amounts in bone. Increased levels of P3NP have been observed during the normal increases in lean mass associated with puberty in adolescent boys and girls, as well as in response to endurance-type exercise in adult males.