## 4 Discussion
Our study suggests that YB could be helpful to accelerate fracture healing, as it is able to promote Runx2, ALP and OC expression, when MSCs are cultured in ODM. Interestingly, the upregulation of OC in cells cultured in basal medium, suggests that also in the presence of a not favorable environment, just like the diabetic tissues, lower doses of YB can make a small but significant contribution to improve bone regeneration. Several studies have demonstrated that MSCs increase the production of ALP only in the presence of osteogenic stimuli [24; 27; 32]. In agreement with these studies, our results showed a huge production of ALP, only in the presence of an osteogenic medium. Contrarily, a lower dose of YB did not show improved ALP activity, compared to the control. However, the Alizarin Red S staining assay highlighted that YB administered at 25 \(\upmu\)g/mL promotes calcium deposition in the short term and long term. A recent study investigates the odonto/osteogenic induction capacity of YB on stem cells from apical papilla [32; 33]. [PERSON] and colleagues reported that YB powder is rich in calcium ions, and it is the main reason for its well-known hemostatic properties. In fact, calcium ions can stimulate the local production of hemostatic agents; moreover, the calcium ions interact with cytokines and growth factors, so stimulating the local bone formation [32; 33; 34; 35]. Mesenchymal stem cells (MSCs) are located in several areas of the human body. Some of them are located in strategic points, in a \"sleeping\" state, waiting for a stimulus able to re-activate them. In the bone marrow, MSCs are richly present, as bone trauma frequently requires a large activation of regenerative processes, to replace the anatomy and the functionality of the area injured by the pathological process. MSCs are also present in strategic tissues of the human organism, such as the oral cavity: These MSCs are often called oral-derived MSCs (OMSCs). OMSCs have been reported to have a remarkable proliferative ability, this can be truly important in such degenerative processes developing on periodontal tissues that can lead to loss of teeth. Interestingly, as a result of this research, it has emerged that YB promotes cell differentiation through the activation of the NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway [35; 36; 37; 38]. However, several differences have been pointed out between that study and our study. Firstly, a different source for MSCs was used; moreover, the YB preparation was highly different, and the time-points we used were longer than the other study. Probably, this is the reason why in our study a 50 \(\upmu\)g/mL concentration of YB did not stimulate cell differentiation, while [PERSON] and colleagues affirmed that it is the best concentration to be used for the experimental sessions on bone healing. In the current literature, no preliminary information has been reported about the use of saponins from YB in bone tissue engineering; nevertheless, it is important to take into consideration this strategic application in the treatment of bone damage [36; 37; 38]. An important field of application of bone regeneration is the dental sciences: In fact, there are several clinical conditions in dentistry requiring proper and timely bone healing, such as periodontal diseases [39], and functional and anatomical rehabilitation after maxillofacial surgery [40; 41]. In this landscape, the authors suggest that future impacting researches should be performed by the scientific community. In more detail, the researchers should investigate on the main translational effects of YB in bone regeneration, as it could have a positive impact on the main regenerative protocols as well as in specific clinical conditions, such as syndromic conditions [42; 43; 44] or oncological conditions [45; 46; 47], or any pathological condition [48; 49; 50] where drugs should be carefully limited.