Gene regulatory network from cranial neural crest cells to osteoblast differentiation and calvarial bone development.

Calvarial bone is one of the most complex sequences of developmental events in embryology, featuring a uniquely transient, pluripotent stem cell-like population known as the cranial neural crest (CNC). The skull is formed through intramembranous ossification with distinct tissue lineages (e.g. neural crest derived frontal bone and mesoderm derived parietal bone). Due to CNC's vast cell fate potential, in response to a series of inductive secreted cues including BMP/TGF-ß, Wnt, FGF, Notch, Hedgehog, Hippo and PDGF signaling, CNC enables generations of a diverse spectrum of differentiated cell types in vivo such as osteoblasts and chondrocytes at the craniofacial level. In recent years, since the studies from a genetic mouse model and single-cell sequencing, new discoveries are uncovered upon CNC patterning, differentiation, and the contribution to the development of cranial bones. In this review, we summarized the differences upon the potential gene regulatory network to regulate CNC derived osteogenic potential in mouse and human, and highlighted specific functions of genetic molecules from multiple signaling pathways and the crosstalk, transcription factors and epigenetic factors in orchestrating CNC commitment and differentiation into osteogenic mesenchyme and bone formation. Disorders in gene regulatory network in CNC patterning indicate highly close relevance to clinical birth defects and diseases, providing valuable transgenic mouse models for subsequent discoveries in delineating the underlying molecular mechanisms. We also emphasized the potential regenerative alternative through scientific discoveries from CNC patterning and genetic molecules in interfering with or alleviating clinical disorders or diseases, which will be beneficial for the molecular targets to be integrated for novel therapeutic strategies in the clinic.

Osteoarthritis versus psoriasis arthritis: Physiopathology, cellular signaling, and therapeutic strategies.

Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological, cellular, and clinical levels. Rheumatologists have marked them as two entirely distinct arthropathies. Given recent discoveries in disease initiation and progression, potential mechanisms, cellular signaling pathways, and ongoing clinical therapeutics, there are now more opportunities for discovering osteoarthritis drugs. This review summarized the osteoarthritis and psoriasis arthritis signaling pathways, crosstalk between BMP, WNT, TGF-ß, VEGF, TLR, and FGF signaling pathways, biomarkers, and anatomical pathologies. Through bench research, we demonstrated that regenerative medicine is a promising alternative for treating osteoarthritis by highlighting significant scientific discoveries on entheses, multiple signaling blockers, and novel molecules such as immunoglobulin new antigen receptors targeted for potential drug evaluation. Furthermore, we offered valuable therapeutic approaches with a multidisciplinary strategy to treat patients with osteoarthritis or psoriasis arthritis in the coming future in the clinic.

Focal adhesion kinase (FAK): its structure, characteristics, and signaling in skeletal system.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase and distributes important regulatory functions in skeletal system. Mesenchymal stem cell (MSC) possesses significant migration and differentiation capacity, is an important source of distinctive bone cells production and a prominent bone development pathway. MSC has a wide range of applications in tissue bioengineering and regenerative medicine, and is frequently employed for hematopoietic support, immunological regulation, and defect repair, although current research is insufficient. FAK has been identified to cross-link with many other keys signaling pathways in bone biology and is considered as a fundamental "crossroad" on the signal transduction pathway and a "node" in the signal network to mediate MSC lineage development in skeletal system. In this review, we summarized the structure, characteristics, cellular signaling, and the interactions of FAK with other signaling pathways in the skeletal system. The discovery of FAK and its mediated molecules will lead to a new knowledge of bone development and bone construction as well as considerable potential for therapeutic use in the treatment of bone-related disorders such as osteoporosis, osteoarthritis, and osteosarcoma.