# Effects of Epigallocatechin-3-O-Gallate on Bone Health
## 3 Biochemical Effects of EGCG
### Increasing the Level of Vascular Endothelial Growth Factor
\begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{**Ref.**} & \multicolumn{2}{c}{**Effects in Cytobiochemistry**} & \multicolumn{1}{c}{**Cell Line/Animal**} & \multirow{2}{*}{**Functional Changes and Methodology**} & \multirow{2}{*}{**Cell Culture Data**} \\ \cline{2-3} \cline{5-5}  & **Influence** & & & \\ \hline \multirow{4}{*}{[32]} & Increasing the expression of & \multirow{2}{*}{hMSCs} & Intracellular signalling genes \(B\)\(\Rightarrow\)2 and \(V\)egf & Solvent EGCG added directly to culture \\  & RUNX2, BMP-2, and VEGF & & were significantly upregulated by stretch, & medium (DMEM-LG, FBS) \\ \cline{2-3} \cline{5-5}  & Acceleration of osteogenic & \multirow{2}{*}{25 uM} & BGCG; TGF-B1 also increased with stretch and & Ostogenic substrate/status. Basal culture \\ \cline{2-3} \cline{5-5}  & differentiation & & stretch with EGCG & medium only; no osteogenic supplements used \\ \hline \multirow{4}{*}{[41]} & Increasing the expression of & \multirow{2}{*}{hGMP-2, RUNX2, ALP, ONC, and GCN mRNA as walls ALP} & \multirow{2}{*}{hBM-MSCs} & \multirow{2}{*}{Transcriptional changes (qPCR):} & Solvent: EGCG stock dissolved in DMSO, \\  & BMC3N & & & & diluted in culture medium before use \\ \cline{2-3} \cline{5-5}  & Activation and mineralization & & & \(B\)\(\)\(\Rightarrow\)2 mRNA increased \(\rightarrow\)459\% & Ostogenic substrate/status Cells cultured in \\ \cline{2-3} \cline{5-5}  & Enhancement of osteogenic & \multirow{2}{*}{1 and 10 uM} & \multirow{2}{*}{1 and 502\%(10 uM) at 48 h} & \multirow{2}{*}{DMEM, \(\beta\)-glycerophosphate} \\ \cline{2-3} \cline{5-5}  & differentiation of hBM-MSCs & & & \\ \hline \multirow{4}{*}{[21]} & Increasing the expression of & \multirow{2}{*}{\begin{tabular}{} \end{tabular} } & Right tibial & \multirow{2}{*}{Key molecular/protein changes:} & Solvent: DMSO \\  & BMP-2 and enhancing bone & & bongs of rats & \(B\)\(\Rightarrow\)2 protein expression (IHC) & Ostogenic substrate/status: Local \\ \cline{2-3} \cline{5-5}  & callus formation & & & \\ \cline{2-3} \cline{5-5}  & Facilitating the healing of & \multirow{2}{*}{\
\begin{tabular}{} \end{tabular} } & 10 uM, & \multirow{2}{*}{EGCG treatment} & \multirow{2}{*}{percutaneous injection at fracture site} \\ \cline{2-3} \cline{5-5}  & & & & \\ \cline{2-3} \cline{5-5}  & Facilitating the healing of & \multirow{2}{*}{
\begin{tabular}{} \end{tabular} } & 10 uM, & \multirow{2}{*}{EGGC treatment} & \multirow{2}{*}{percutaneous injection at fracture site} \\ \cline{2-3} \cline{5-5}  & fractures of the tibia & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 4: _Cont._in osteoblast-like MC3T3-E1 cells could lead to an increase in PGF\({}_{2a}\)-stimulated VEGF synthesis in osteoblast-like MC3T3-E1 cells and thus regulate capillary endothelial cell proliferation [56]. In another study performed on hMSCs with EGCG combined with mechanical stretching, it was shown that increasing the expression of RUNX2, BMP-2, and VEGF leads to an acceleration of osteogenic differentiation [32]. In another in vivo study, it was presented that the implantation of EGCG-modified collagen membrane results in an increase in the number of macrophages (M2), promotes the secretion of VEGF and BMP-2, and increases the expression of RUNX-2 and OPN. It is interesting because the collagen membrane could be used in guided bone regeneration (GBR), acting as a barrier to prevent the migration of epithelial cells and connective tissue, as well as it could maintain space for bone regeneration, and promote important biological activities including cell adhesion, proliferation, migration, and differentiation [45].