Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

Abstract

Vital osteocytes have been well known to function as an important orchestrator in the preservation of robustness and fidelity of the bone remodeling process. Nevertheless, some key pathological factors, such as sex steroid deficiency and excess glucocorticoids, and so on, are implicated in inducing a bulk of apoptotic osteocytes, subsequently resulting in resorption-related bone loss. As much, osteocyte apoptosis, under homeostatic conditions, is in an optimal state of balance tightly controlled by pro- and anti-apoptotic mechanism pathways. Importantly, there exist many essential signaling proteins in the process of osteocyte apoptosis, which has a crucial role in maintaining a homeostatic environment. While increasing in vitro and in vivo studies have established, in part, key signaling pathways and cross-talk mechanism on osteocyte apoptosis, intrinsic and complex mechanism underlying osteocyte apoptosis occurs in various states of pathologies remains ill-defined. In this review, we discuss not only essential pro- and anti-apoptotic signaling pathways and key biomarkers involved in these key mechanisms under different pathological agents, but also the pivotal role of apoptotic osteocytes in osteoclastogenesis-triggered bone loss, hopefully shedding new light on the attractive and proper actions of pharmacotherapeutics of targeting apoptosis and ensuing resorption-related bone diseases such as osteoporosis and fragility fractures.

Chrysin induces autophagy through the inactivation of the ROS‑mediated Akt/mTOR signaling pathway in endometrial cancer

“…Thus, it was concluded that, in the process of cancer progression, the analysis of ROS level fluctuation may be of importance for cancer prevention and treatment. Furthermore, autophagy is triggered in response to all types of biological stress, including increased oxidative stress ( 40 ). The fluorescence microscopy results of the present study revealed that NAC pretreatment may act as an antioxidant which remarkably inhibits ROS production and the transition from LC3I to LC3II in treated cells, thus suggesting that NAC exhibited a considerable blocking effect on chrysin-induced autophagy.…”

Osteoblast cell death triggers a pro-osteogenic inflammatory response regulated by reactive oxygen species and glucocorticoid signaling in zebrafish

“…The consequences of isolated osteoblast death during homeostasis and medical treatment, as well as their replacement, are not particularly clear. In recent years, osteocytes have gained center stage as sensors of biomechanical strain and players in modeling and remodeling of bone (BONEWALD, 2007;Kennedy et al, 2012;Ru & Wang, 2020). However, osteoblasts, mirroring the pre-osteocytic cell stage, have suggested to play a similar role in sensation of microscopic tissue damage.…”

Osteoporosis drug treatment after fracture

“…показали в исследованиях на крысах, что лечение антителами к склеростину ускоряет образование кости и костной массы, а также положительно влияет на увеличение ее прочности [34]. Кроме того, есть мнение, что кость, образовавшаяся при блокировании склеростина, впоследствии не истощается в результате снижения функциональной активности, по крайней мере, на ранней стадии [35]. Таким образом, позитивные результаты изучения механизма действия склеростина и его подавления различными препаратами могут быть применены в реальной клинической практике для достижения ускоренной консолидации перелома.…”