YAP1 inhibits the induction of TNF-α-stimulated bone-resorbing mediators by suppressing the NF-κB signaling pathway in MC3T3-E1 cells.

Yes-associated protein 1 (YAP1), the core downstream effector of the Hippo signaling cascade, was involved in the regulation of osteoblast and osteoclast differentiation and in bone metabolism. However, the regulatory effects and mechanisms of YAP1 on bone-remodeling molecules in osteoblasts under inflammation remain unknown. In this study, YAP1 expression level was downregulated after treatment with inflammatory cytokine tumor necrosis factor-α (TNF-α) in MC3T3-E1 cells. The key osteoclastogenic molecules induced by TNF-α, namely, interleukin-6 and receptor activator of nuclear factor-κB (NF-κB) ligand, were suppressed after lentivirus-induced YAP1 overexpression, which dramatically increased the expression level of osteoprotegerin. Conversely, the expression levels of the above factors showed opposite trends in the YAP1 small interfering RNA and YAP1 inhibitor (verteporfin) group. Mechanistically, YAP1 attenuated the TNF-α-induced activation of the NF-κB signaling pathway as revealed by the reduced expression of phosphorylated-p65 and NF-κB reporter activity and the nuclear translocation of p65. Moreover, the expression level of YAP1 suppressed by TNF-α was reversed by berberine in concentration-dependent manner. Taken together, our study suggests that YAP1 plays a critical role in the regulation of bone metabolism and is a potential therapeutic target for treating inflammatory bone resorption.

Creeping attachment: A literature review.

OBJECTIVE: Mucogingival surgery has been widely applied in clinics. An interesting phenomenon after mucogingival surgery is the coronal migration of gingival margin, which is described as "creeping attachment." The goal of this review is to summarize the characteristics, significance, mechanism, and manifestation of the creeping attachment after mucogingival surgery and to describe the factors associated with its occurrence. OVERVIEW: A total of 82 relevant articles were included in the literature review. The characteristics and significance of the creeping attachment after mucogingival surgery were analyzed. The mechanism of the creeping attachment was explored. Different manifestations of and factors associated with creeping attachment were summarized. CONCLUSIONS: Creeping attachment may occur to obtain additional root coverage after the healing of various mucogingival surgeries. However, this coverage is not always complete nor entirely predictable. CLINICAL SIGNIFICANCE: Creeping attachment plays an important role in the prognosis of mucogingival surgeries. This review will help clinicians get a thorough recognition and understanding of this phenomenon.

YAP1 influences differentiation of osteoblastic MC3T3-E1 cells through the regulation of ID1.

Yes-associated protein 1 (YAP1) transcriptional coactivator has recently been identified to regulate skeletal lineage cell differentiation and bone development. However, the role and molecular mechanisms of YAP1 in the regulation of osteoblastic differentiation remains to be elucidated. In this study, we demonstrated that YAP1 expression was increased during osteogenic differentiation of rat bone mesenchymal stem cells and MC3T3-E1. YAP1 overexpression MC3T3-E1 showed increased expression of osteogenesis markers, such as runt-related transcription factor 2, osteocalcin, and osteopontin, as well as alkaline phosphatase and alizarin red staining. Conversely, YAP1 knockdown significantly suppressed MC3T3-E1 osteoblastic differentiation. Mechanistically, we found that YAP1 overexpression upregulated the mRNA and protein expression of the inhibitor of differentiation/DNA binding 1 (ID1), which was contrary to the results of YAP1-knockdown group. Moreover, the early osteogenic differentiation of MC3T3-E1 cells was enhanced by ID1 overexpression. Furthermore, transient transfection with exogenous ID1 overexpression plasmid completely recaptured the decreased effects of YAP1 knockdown on MC3T3-E1 cell differentiation. In addition, ß-catenin and AMP-activated protein kinase signaling pathways participated in YAP1 regulation processes. Taken together, our study suggests that YAP1 is a crucial modulator of osteoblast differentiation in vitro, and provides insight into the mechanism by which YAP1 regulates osteoblast differentiation.

The effect of respiratory capacity for dose sparing in left-sided breast cancer irradiation with active breathing coordinator technique.

Background and aim: A subsequent cardiac toxicity is deemed to be dose-dependent for left-sided breast cancer irradiation. This study aims to demonstrate the effect of respiratory capacity for dose sparing when the deep inspiration breath hold with Active Breathing Coordinator technique (ABC-DIBH) is used in left-sided breast cancer irradiation. Methods: 74 left-sided breast cancer patients, who received whole breast or post-mastectomy chest wall radiotherapy with ABC-DIBH between 2020 and 2021 in our center, were retrospectively reviewed in this study. CT scans of free breath (FB) and ABC-DIBH were done for each patient, and two treatment plans with a prescription dose of 5000 cGy/25 Fr were designed separately. The dose to heart, left anterior descending artery (LAD) and lungs was compared between FB and ABC-DIBH. The correlation between individual parameters (dose to organs at risk (OARs) and minimum heart distance (MHD)) was analyzed, and the effect of respiratory capacity for dose sparing was assessed. Results: The plans with ABC-DIBH achieved lower Dmean for heart (34.80%, P < 0.01) and LAD (29.33%, P < 0.01) than those with FB. Regression analysis revealed that both Dmean and D2 of heart were negatively correlated with MHD in the plans with FB and ABC-DIBH, which decreased with the increase in MHD by 37.8 cGy and 309.9 cGy per 1mm, respectively. Besides, a lower Dmean of heart was related to a larger volume of ipsilateral lung in plans with FB. With the increase in volume of ipsilateral lung, the linear correlation was getting weaker and weaker until the volume of ipsilateral lung reached 1700 cc. Meanwhile, a negative linear correlation between Dmean of LAD and MHD in plans with FB and ABC-DIBH was observed, whose slope was 162.5 and 135.9 cGy/mm, respectively. Furthermore, when the respiratory capacity of ABC-DIBH reached 1L, and the relative ratio (ABC-DIBH/FB) reached 3.6, patients could obtain the benefit of dose sparing. The larger difference in respiratory capacity had no significant effect in the larger difference of MHD, Dmean of heart and Dmean of LAD between FB and ABC-DIBH. Conclusion: This study demonstrates the sufficiently good effect of ABC-DIBH when utilizing for cardiac sparing. It also reveals the correlations among individual parameters and the effect of respiratory capacity for dose sparing. This helps take optimal advantage of the ABC-DIBH technique and predict clinical benefits.

[Clinical observation on effect of shenqi fanghou recipe in preventing and treating radiation injury in patients with head and neck tumor].

OBJECTIVE: To observe the therapeutic effect of shenqi fanghou recipe (SFR) in preventing and treating radiation injury in patients with head and neck tumor. METHODS: One hundred and forty patients with head and neck tumor, including nasopharyngeal carcinoma, carcinoma of tonsil or tongue, were randomly divided into 2 groups, 70 patients in the observed group were given modified SFR as adjuvant to radiotherapy, while 70 patients in the control group were treated with radiotherapy alone. The radiation reactions during radiotherapy and the condition of late stage radiation injury radiotherapy in patients in the 2 groups were observed. RESULTS: The degree of oropharyngeal mucosa reaction, dryness in mouth and radiation dermatitis in cervical region in the observed group was milder than those in the control group, and the radiation injury induced late stage sequelae, such as the degree of mouth-opening was better and the cervical muscular sclerosis was better in the observed group than in the control group, showing significant difference (P < 0.01). CONCLUSION: SFR has definite effect in preventing and treating radiation reaction and late stage radiation injury in patients with head and neck tumor.