Background: The aim of this review is to present the available evidence regarding the effectiveness of different regenerative approaches for the treatment of furcation defects in specific clinical scenarios compared with conventional surgical therapy to provide clinical guidelines for the therapeutic management of furcation defects and to identify priorities for future research that may advance the understanding of periodontal regenerative medicine.Methods: A comprehensive search based on predetermined eligibility criteria was conducted to identify human original studies and systematic reviews on the topic of periodontal regeneration of furcation defects. Two reviewers independently screened the title and abstract of the entries yielded from the initial search. Subsequently, both reviewers read the full‐text version of potentially eligible studies, made a final article selection, and extracted the data of the selected studies considering specific clinical scenarios. The clinical scenarios contemplated in this review included the following: 1) facial and interproximal Class I defects in maxillary molars; 2) facial and lingual Class I defects in mandibular molars; 3) facial and interproximal Class II furcation defects in maxillary molars; 4) facial and lingual Class II furcation defects in mandibular molars; 5) Class III furcation defects in maxillary molars; 6) Class III furcation defects in mandibular molars; and 7) Class I, II, or III furcation defects in maxillary premolars. Endpoints of interest included different clinical, radiographic, microbiologic, histologic, and patient‐reported outcomes.Results: The initial search yielded a total of 1,500 entries. The final selection consisted of 150 articles, of which six were systematic reviews, 109 were clinical trials, 27 were case series, and eight were case reports. A summary of the main findings of previously published systematic reviews and the available evidence relative to the indication of regenerative approaches for the treatment of furcation defects compared with conventional surgical therapy are presented. Given the marked methodologic heterogeneity and the wide variety of materials and techniques applied in the selected clinical trials, the conduction of a meta‐analysis was not viable.Conclusions: On the basis of the reviewed evidence, the following conclusions can be drawn. 1) Periodontal regeneration has been demonstrated histologically and clinically for the treatment of maxillary facial or interproximal and mandibular facial or lingual Class II furcation defects. 2) Although periodontal regeneration has been demonstrated histologically for the treatment of mandibular Class III defects, the evidence is limited to one case report. 3) Evidence supporting regenerative therapy in maxillary Class III furcation defects in maxillary molars is limited to clinical case reports. 4) In Class I furcation defects, regenerative therapy may be beneficial in certain clinical scenarios, although most Class I furcation defects may be successfully treated with non‐regenerative therapy. 5) Future research efforts should be primarily directed toward the conduction of clinical trials to test novel regenerative approaches that place emphasis primarily on patient‐reported outcomes and also on histologic demonstration of periodontal regeneration. Investigators should also focus on understanding the influence that local, systemic, and technical factors may have on the outcomes of regenerative therapy in furcation defects.

Background: Musashi-1 (MSI1) is a negative regulator of mesenchymal stromal cell (MSC) differentiation which in turn favors cell proliferation. However, little is known about its expression by MSC from the oral cavity and in the context of osteogenic differentiation. Aim: The aim of this study was to analyze the expression of MSI1 in the context of osteogenic differentiation of MSC derived from the oral cavity. Material/methods: For this in vitro study, MSC were isolated from six different origins of the oral cavity. They were extensively characterized in terms of proliferative and clonogenicity potential, expression of stemness genes (MYC, NANOG, POU5F1, and SOX2), expression of surface markers (CD73, CD90, CD105, CD14, CD31, CD34, and CD45) and adipo-, chondro- and osteogenic differentiation potential. Then, osteogenic differentiation was induced and the expression of MSI1 mRNA and other relevant markers of osteogenic differentiation, including RUNX2 and Periostin, were also evaluated. Results: Cell populations from the alveolar bone (pristine or previously grafted with xenograft), dental follicle, dental germ, dental pulp, and periodontal ligament were obtained. The analysis of proliferative and clonogenicity potential, expression of the stemness genes, expression of surface markers, and differentiation potential showed similar characteristics to those of previously published MSC from the umbilical cord. Under osteogenic differentiation conditions, all MSC populations formed calcium deposits and expressed higher SPARC. Over time, the expression of MSI1 followed different patterns for the different MSC populations. It was not significantly different than the expression of RUNX2. In contrast, the expression of MSI1 and POSTN and RUNX2 were statistically different in most MSC populations. Conclusion: In the current study, a similar expression pattern of MSI1 and RUNX2 during in vitro osteogenic differentiation was identified.

This study aimed to analyze the expression of Musashi-1 (MSI1) in maxillary native bone and grafted bone after maxillary sinus floor elevation. To do so, fifty-seven bone biopsies from 45 participants were studied. Eighteen samples were collected from native bone while 39 were obtained 6 months after maxillary sinus grafting procedures. Musashi-1 was analyzed by immunohistochemistry and RT-PCR. MSI1 was detected in osteoblasts and osteocytes in 97.4% (38/39) of grafted areas. In native bone, MSI1 was detected in only 66.6% (12/18) of the biopsies, mainly in osteocytes. Detection of MSI1 was significantly higher in osteoprogenitor mesenchymal cells of grafted biopsies (p < 0.001) but minor in smooth muscle and endothelial cells; no expression was detected in adipocytes. The mesenchymal cells of the non-mineralized tissue of native bone showed very low nuclear expression of MSI1, in comparison to fusiform cells in grafted areas (0.28(0.13) vs. 2.10(0.14), respectively; p < 0.001). Additionally, the detection of MSI1 mRNA was significantly higher in biopsies from grafted areas than those from native bone (1.00(0.51) vs. 60.34(35.2), respectively; p = 0.029). Thus, our results regardig the significantly higher detection of Musashi-1 in grafted sites than in native bone reflects its importance in the remodeling/repair events that occur after maxillary sinus floor elevation in humans.