RESUMO
The primary cilium is a hair-like projection that controls cell development and tissue homeostasis. Although accumulated studies identify the molecular link between cilia and cilia-related diseases, the underlying etiology of ciliopathies has not been fully understood. In this paper, we determine the function of Rab34, a small GTPase, as a key regulator for controlling ciliogenesis and type I collagen trafficking in craniofacial development. Mechanistically, Rab34 is required to form cilia that control osteogenic proliferation, survival, and differentiation via cilia-mediated Hedgehog signaling. In addition, Rab34 is indispensable for regulating type I collagen trafficking from the ER to the Golgi. These results demonstrate that Rab34 has both ciliary and non-ciliary functions to regulate osteogenesis. Our study highlights the critical function of Rab34, which may contribute to understanding the novel etiology of ciliopathies that are associated with the dysfunction of RAB34 in humans.
Assuntos
Cílios , Osteogênese , Proteínas rab de Ligação ao GTP , Cílios/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , Animais , Camundongos , Humanos , Crânio/metabolismo , Proteínas Hedgehog/metabolismo , Diferenciação Celular , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Transdução de Sinais , Desenvolvimento Ósseo , Ossos Faciais/metabolismo , Ossos Faciais/crescimento & desenvolvimento , Ossos Faciais/embriologia , Proliferação de Células , Transporte Proteico , Complexo de Golgi/metabolismoRESUMO
Proteomics is a growing field that offers insights into various aspects of disease processes and therapy responses. Within the field of orthopedics, there are a variety of diseases that have a poor prognosis due to a lack of targeted curative therapy or disease modifying therapy. Other diseases have been difficult to manage in part due to lack of clinical biomarkers that offer meaningful insight into disease progression or severity. As an emerging technology, proteomics has been increasingly applied in studying bone biology and an assortment of orthopedics related diseases, such as osteoarthritis, osteosarcoma and bone tumors, osteoporosis, traumatic bone injury, spinal cord injury, hip and knee arthroplasty, and fragile healing. These efforts range from mechanistic studies for elucidating novel insights in tissue activity and metabolism to identification of candidate biomarkers for diagnosis, prognosis, and targeted treatment. The knowledge gained from these proteomic and functional studies has provided unique perspectives in studying orthopedic diseases. In this review, we seek to report on the current state of the proteomic study in the field of orthopedics, overview the advances in clinically applicable discoveries, and discuss the opportunities that may guide us for future research.