# Effects of Epigallocatechin-3-O-Gallate on Bone Health
## 3 Biochemical Effects of EGCG
### Induction of Caspase-3  
Both programmed cell death mechanisms in the human body--apoptosis and pyproptosis (an inflammatory form of cell death)--are caspase-dependent pathways. Caspases are a family of cysteine-dependent proteases that are synthesised as inactive zymogens. They are activated by dimer formation (e.g., apoptotic initiator caspases-8, -9) or by cleavage (e.g., apoptotic effector caspase-3) [119]. Caspase-3 cleaves a series of substrates and activates an endonuclease, leading to DNA fragmentation that is the hallmark of apoptosis [120]. In their overview of caspases, [PERSON] et al. [121] state that these proteases play not only a key role in apoptosis and inflammation, but also are multifunctional enzymes with lethal and non-lethal functions. According to recent findings, caspases are localised subcellularly. These enzymes have to be transported into the nucleus for central caspase-3 to regulate the apoptotic disintegration of the nucleus. In fact, it was discovered that activated caspase-3 is localised in the nucleus of cells during apoptosis [122]. In the case of non-apoptotic processes, it is proposed that caspase activation is locally held in subcellular compartments, leading to the availability of specific substrates. Caspase-3 is typically localised in the cytoplasm of intact cells. Another method of non-apoptotic engagement could involve sub-lethal caspase activation. This may be related to a phenomenon known as mitochondrial outer membrane permeabilization (MOMP); specifically, a subtype referred to as \"minority MOMP\". This effect supposes that a part of the cell mitochondria is permeable. Initially, the phenomenon was discovered to trigger apoptosis via rapid caspase activation. Minority MOMP reduced caspase activation, which is insufficient to trigger cell death [123]. Instead, this caspase activity damages DNA, resulting in increased genomic instability [121; 124].  
The therapeutic use of caspase-3 in the treatment of several illnesses, including cancer, heart failure, and neurological disorders, has significantly increased to date [125]. [PERSON] et al. [126], in the review article, provided follow-up data about the remarkable impact of caspase-3 ferment inhibition by EGCG due to the reduction of cell apoptosis and restoration of mitochondrial membrane potential. Therefore, EGCG could be useful for preventing cardiovascular diseases characterised by endothelial dysfunction [127], as well as neurological diseases and models with injuries in primary retinal pigment epithelial cells [128; 129].  
Chondrosarcoma is a malignant tumour of cartilage tissue. [PERSON] et al. showed in an in vitro study that EGCG significantly reduced the viability of HTB-94 human chondrosarcoma cells by activating caspase-3/CPP32-like proteases and promoting apoptosis [60]. In another study performed on the murine monocyte/macrophage cell line, Raw 264.7, it was noted that DNA fragmentation and the induction of the activation of caspase-3 in RAW 264.7 cell-derived osteoclasts could lead to osteoclast apoptosis caused in part by caspase-3 and thus the prevention of alveolar bone resorption [46].