JAK/STAT pathway and molecular mechanism in bone remodeling
- PDF / 661,980 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 84 Downloads / 209 Views
REVIEW
JAK/STAT pathway and molecular mechanism in bone remodeling Eliana Rita Sanpaolo1 · Cinzia Rotondo1 · Daniela Cici1 · Ada Corrado1 · Francesco Paolo Cantatore1 Received: 21 July 2020 / Accepted: 10 October 2020 © The Author(s) 2020
Abstract JAK/STAT signaling pathway is involved in many diseases, including autoimmune diseases, which are characterized by a close interconnection between immune and bone system. JAK/STAT pathway is involved in bone homeostasis and plays an important role in proliferation and differentiation of some cell types, including osteoblasts and osteoclasts. Different molecules, such as cytokines, hormones, and growth factors are responsible for the activation of the JAK/STAT pathway, which leads, at the nuclear level, to start DNA transcription of target genes. Bone cells and remodeling process are often influenced by many cytokines, which act as strong stimulators of bone formation and resorption. Our aim, through careful research in literature, has been to provide an overview of the role of the JAK/STAT pathway in bone remodeling and on bone cells, with a focus on cytokines involved in bone turnover through this signal cascade. The JAK/STAT pathway, through the signal cascade activation mediated by the interaction with many cytokines, acts on bone cells and appears to be involved in bone remodeling process. However, many other studies are needed to completely understand the molecular mechanism underlying these bone process. Keywords JAK/STAT pathway · Bone · Osteoblast · Osteoclast · Cytokine
Introduction The Janus kinases (JAKs) are a family of protein tyrosine kinases (PTKs), named JAK1, JAK2, JAK3, and TYK2, that act on signal transducer and activator of transcription (STAT). The expression of JAK3 appears to be mainly in the hematopoietic cells. In contrast, the expression of the other members, JAK1, JAK2, and TYK2, is ubiquitous. Eliana Rita Sanpaolo, Cinzia Rotondo have contributed equally to the achievement of the manuscript. * Eliana Rita Sanpaolo [email protected] Cinzia Rotondo [email protected] Daniela Cici [email protected] Ada Corrado [email protected] Francesco Paolo Cantatore [email protected] 1
Department of Medical and Surgical Sciences, Rheumatology Clinic, University of Foggia Medical School, Foggia, Italy
After their activation, JAKs induce the phosphorylation of some STAT elements in the cytoplasm, which, subsequently their dimerization, are translocated in the nucleus. In the nucleus, STAT dimers bind to specific areas of DNA leading to the regulation of target genes responsible for the regulation of migration, proliferation, and apoptosis [1–3]. JAK/ STAT signaling pathway (Fig. 1) plays a key role in several cytokines, immune system regulators, hormones, and hematopoiesis factors [4]. A specific receptor is located on the surface of target cells that bind specific cytokines. These receptors, which can be composed of multiple subunits, are substantially associated with JAK monomer [5–9]. Initially, the JAK monomers
Data Loading...
