# Effects of Epigallocatechin-3-O-Gallate on Bone Health
## 3 Biochemical Effects of EGCG
### Increasing Expression of the OSL
The most important class of biomolecules in bone regeneration is the BMP [91]. These proteins can regulate the function and differentiation of cells involved in bone formation and healing [92; 93; 94]. BMP-2 is an exceptionally potent growth factor that acts as a chemoattractant for mesenchymal stromal cells, rapidly inducing their differentiation into osteoblasts while also supporting their viability. BMP-2 is the most potent molecule in osteoinduction, essential for new bone formation [91]. The differentiation of mesenchymal cells into osteoblast precursors is induced by BMP-2 and has a beneficial effect on osteoblast maturation by increasing the expression of RUNX2 and osteoblast marker genes [95]. [PERSON] et al. [92] reported that besides inducing bone growth, BMP-2 and other BMPs stimulated the increase of VEGF in the bone formation process. During skeletal development,  
\begin{table}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{**Ref. **} & **Effects in Cytobiochemistry** & **Cell Line** & **Functional Changes and Methodology** & **Cell Culture Data** \\ \cline{2-4}  & **Influence** & **EGCG Conc. ** & & \\ \hline \multirow{4}{*}{[26]} & Increasing the expression of osteogenic genes and elevating & \multirow{4}{*}{D1} & Transcriptional changes & \begin{tabular}{c} Solvent; EGCG dissolved in DMSO stock, \\ diluted in culture medium before use \\ Osteogenic substrate/status Cells cultured in \\ dexamethasone/s \\ \end{tabular}  \\  & & & (emi-quantitative RT-PCR): Osr mRNA & \begin{tabular}{c} Osteogenic substrate/status Cells cultured in \\ dose/s \\ \end{tabular}  \\  & & & (i nM) and 137\% (10 nM) & \begin{tabular}{c} DMEM, FBS, sodium ascorbate, and antibiotics; \\ - \\ and mineralisation assays \\ \end{tabular}  \\ \hline \multirow{4}{*}{[29]} & Increasing ALP activity and mRNA and protein expression levels of CO1, RUNX2, OPN, and OSX & \multirow{4}{*}{hPDLCs} & \begin{tabular}{c} Transcriptional changes: RUNX2, CO1, and \\ with \(\sim\)8 nM of EGCG, peaking at 6 nM for \\ tRNAX2, CO1, and OSX \\ Protein expression changes (Western blot): \\ OPN/ OSX proteins upregulated at 6 nM \\ of EGCG; 10 nM of EGCG decreased the OSX \\ protein compared to control \\ \end{tabular}  & \begin{tabular}{c} Solvent; Dissolved in distilled water as stock, \\ diluted in culture medium before use \\ Osteogenic substrate/status Cells cultured in \\ osteogenic differentiation mechanism containing \\ \(\alpha\)-MEM, FBS, antibiotics, L-ascorbic acid, \\ dexamethasone/s, \(\beta\)-glycerphosphate \\ \end{tabular}  \\ \hline \multirow{4}{*}{[33]} & Increasing ALP activity/mineralisation and & \multirow{4}{*}{ \begin{tabular}{c} hBM-MSCs \\ INFNe (1-20 ng/mL) dose-dependently \\ decreased _Runx2_ and _Oss_ expression up to \\ -20% at 5 mg/mL. more at higher doses; EGCG \\ (5 and 10 nM) reversed \\ inflammation of human \\ inflammation of ECCC \\ \end{tabular}  } & \ \begin{tabular}{c} Transcriptional changes: SUNX2; ECCC used at specified micromolar \\ concentrations diluted in \\ culture/differentiation media \\ (5 and 10 nM) \\ \end{tabular}  \\  & & \begin{tabular}{c} Categorical substrate/status Cells induced to \\ differentiate using osteogenic medium \\ containing \(\beta\)-glycer phosphate, \\ dexamethasone/s, \(\beta\)-glycerphosphate \\ \end{tabular}  \\  & & & \\ \hline \multirow{4}{*}{[33]} & \multicolumn{4}{c}{Abbreviations: ALP—alkaline phosphatase; COLL—collagen type 1; D1— murine bone marrow mesenchymal stem cell line; DMSO—dimethyl sulfoxide; FBS  
BMPs and Wnts have been implicated in the specification of osteo/chondro progenitors and remain involved in each of the subsequent stages of endochondral ossification through the regulation of RUNX2 and OSX expression [93]. BMPs can activate RUNX2, and BMP-2 has been shown to activate OSX in RUNX2 mutant cells, but whether this is direct or mediated through \(\beta\)-catenin is not certain [93,96]. Another possible mechanism by which BMP-2 may act is through the levels of Smad1, a BMP-specific transcription factor.