Tyrosine Kinase Src Is a Regulatory Factor of Bone Homeostasis

Abstract

Osteoclasts, which resorb the bone, and osteoblasts, which form the bone, are the key cells regulating bone homeostasis. Osteoporosis and other metabolic bone diseases occur when osteoclast-mediated bone resorption is increased and bone formation by osteoblasts is decreased. Analyses of tyrosine kinase Src-knockout mice revealed that Src is essential for bone resorption by osteoclasts and suppresses bone formation by osteoblasts. Src-knockout mice exhibit osteopetrosis. Therefore, Src is a potential target for osteoporosis therapy. However, Src is ubiquitously expressed in many tissues and is involved in various biological processes, such as cell proliferation, growth, and migration. Thus, it is challenging to develop effective osteoporosis therapies targeting Src. To solve this problem, it is necessary to understand the molecular mechanism of Src function in the bone. Src expression and catalytic activity are maintained at high levels in osteoclasts. The high activity of Src is essential for the attachment of osteoclasts to the bone matrix and to resorb the bone by regulating actin-related molecules. Src also inhibits the activity of Runx2, a master regulator of osteoblast differentiation, suppressing bone formation in osteoblasts. In this paper, we introduce the molecular mechanisms of Src in osteoclasts and osteoblasts to explore its potential for bone metabolic disease therapy.

Mapping human disease-associated enzymes into Reactome allows characterization of disease groups and their interactions

“…Osteoporosis is a disorder characterized by the deterioration of the bone tissue, and mainly due to the impairment of bone homeostasis, where SRC plays a central role (it promotes bone resorption by osteoclasts and suppresses bone formation by osteoblasts 9 ), as it is also described in the Reactome pathway R-HAS-8940973 (RUNX2 regulates osteoblast differentiation).…”

Expression of Src kinase in hypertrophic cardiomyocytes of the left ventricle of exercising rats

“…Among the many signaling pathways involved in cardiac hypertrophy, Src proteins are mainly involved in integrin and G proteincoupled receptor-mediated signaling pathways [11] . A related study shows that knockdown of Src kinase attenuates myocardial brosis and cardiac hypertrophy in vaso-activated mice [12] . This study con rmed the involvement of Src kinase in the hypertrophic process of exercising cardiomyocytes by immunohistochemistry, providing important information for further studies of the exercising heart.…”

Icariin regulates RANKL-induced osteoclast differentiation via the ERα/c-Src/RANK signaling

“…C-Src is a key tyrosine kinase in osteoclasts that regulates ruffling formation, bone cell adhesion, and bone resorption [22]. Park et al found that the link of c-Src to the RANK signaling cascade is essential for osteoclasts to resorb bone [23].…”