KAT7 enhances the proliferation and metastasis of head and neck squamous carcinoma by promoting the acetylation level of LDHA.

Lysine acetyltransferase 7 (KAT7), a histone acetyltransferase, has recently been identified as an oncoprotein and has been implicated in the development of various malignancies. However, its specific role in head and neck squamous carcinoma (HNSCC) has not been fully elucidated. Our study revealed that high expression of KAT7 in HNSCC patients is associated with poor survival prognosis and silencing KAT7 inhibits the Warburg effect, leading to reduced proliferation, invasion, and metastatic potential of HNSCC. Further investigation uncovered a link between the high expression of KAT7 in HNSCC and tumor-specific glycolytic metabolism. Notably, KAT7 positively regulates Lactate dehydrogenase A (LDHA), a key enzyme in metabolism, to promote lactate production and create a conducive environment for tumor proliferation and metastasis. Additionally, KAT7 enhances LDHA activity and upregulates LDHA protein expression by acetylating the lysine 118 site of LDHA. Treatment with WM3835, a KAT7 inhibitor, effectively suppressed the growth of subcutaneously implanted HNSCC cells in mice. In conclusion, our findings suggest that KAT7 exerts pro-cancer effects in HNSCC by acetylating LDHA and may serve as a potential therapeutic target. Inhibiting KAT7 or LDHA expression holds promise as a therapeutic strategy to suppress the growth and progression of HNSCC.

The effect of oestrogen on mandibular condylar cartilage via hypoxia-inducible factor-2α during osteoarthritis development.

Oestrogen and hypoxia inducible factor-2α (HIF2α) are key regulators in the pathogenesis of osteoarthritis (OA). However, the cellular interaction between oestrogen and HIF2α in articular cartilage during OA process remains unknown. Our previous study has revealed that high-physiological level of oestrogen aggravates the degradation of condylar cartilage in the early stage of temporomandibular joint osteoarthritis (TMJ OA). Here, we hypothesize that HIF2α involves the effect of oestrogen on mandibular condylar cartilage in the progression of TMJ OA. Our experiment in vivo found that the degeneration of condylar cartilage caused by unilateral anterior crossbite (UAC) model, characterized by obvious degenerative morphology, loss of cartilage extracellular matrix, up-regulation of TNF-α, HIF2α and its' down-stream OA-related cytokines (MMP-13, VEGF and Col X), could be alleviated by lack of oestrogen while aggravated by high level of oestrogen in rats. Meanwhile, our in vitro study found that 17ß-estradiol stimulation resulted in the loss of extracellular matrix, increased expression of TNF-α, IL-1, HIF2α and its' down-stream OA-related cytokines (MMP-13, VEGF and Col X) in primary condylar chondrocytes via oestrogen receptor beta (ERß), which could be reversed by ER antagonist, selective estrogen receptor modulators (SERMs) and HIF2α translation inhibitor. Our results reveal that high level of oestrogen can aggravate the degenerative changes of mandibular condylar cartilage, while lack of oestrogen can alleviate it via oestrogen-ERß-HIF2α pathway during TMJ OA progression.

The effects of age and sex on the expression of oestrogen and its receptors in rat mandibular condylar cartilages.

OBJECTIVE: Oestrogen expression may indicate a difference in resistance potential to mechanical strain. The purpose of this study was to investigate the expression of oestrogen and oestrogen receptors in mandibular condylar cartilages in male and female Sprague-Dawley rats at different ages. MATERIALS AND METHODS: One-hundred SD rats at the age of 2, 4, 8 weeks and 4, 12 months in both sexes, 10 in each age-sex group, were enrolled in this study. The expression of oestradiol, ERalpha and ERbeta was detected in mandibular condylar cartilages by the method of immunohistochemistry, and enzyme-linked immunosorbent assay or western blot. RESULTS: Oestradiol and ERs immunoreactivity were obvious in mandibular condylar cartilages of SD rats. Oestradiol and ERalpha were observed in hypertrophic and mature layers, while ERbeta only in hypertrophic layer. There was no sex difference of same age (except 8-week age group) in the expression of oestradiol. The expression of both ERs, however, was usually higher in male than in age-matched female rats (P<0.05), except that the 8-week-old female rats showed a higher ERalpha expression and the 4- and 8-week-old female rats showed a higher ERbeta expression than the age-matched male ones in western blot results (P<0.05). CONCLUSIONS: The results that oestradiol, ERalpha and ERbeta are co-expressed in rat mandibular condylar cartilage, indicate that mandibular condylar cartilage is a target for oestrogen. The age and sex related differences in ERs expression may indicate a difference in potential to resist mechanical loading between genders at different ages.

Locally synthesized estrogen plays an important role in the development of TMD.

Estrogens have been suggested to play an important role in the development of temporomandibular disorders (TMD). However, a growing body of epidemiological, clinical and experimental researches focusing on the relationship between TMD and exogenous estrogen or serum estrogen has produced conflicting results. Recently, locally synthesized estrogens have been found and proved to contribute greatly to the function of cartilage. We hypothesize that estrogens synthesized locally in condylar cartilage have a profound effect on the development of TMD. Future investigation of local estrogen in condylar cartilage may give, at least partially, valuable evidences for the etiology and treatment strategy of TMD. In our opinion, regulating the amount and effect of locally synthesized estrogen seems to hold interesting future prospects for the treatment of TMD.

Odontogenic potential of mesenchymal cells from hair follicle dermal papilla.

Dental pulp stem cells from teeth can be used for tooth regeneration. Although nondental stem cells derived from bone marrow can differentiate into odontoblast-like cells when recombined with embryonic oral epithelium, these cells can lose their ability to differentiate after an extended number of cell culture passages. There has been limited research to identify stem cells from other tissue sources to regenerate teeth. As another candidate source for mesenchymal stem cells, hair follicle has obtained much more attention recently because of its easy accessibility. In this study, cultured vibrissae follicle dermal papilla mesenchymal cells (FDPMCs) from adult C57BL/6 GFP mice can differentiate into adipocytes and osteoblasts in vitro. Moreover, in the inductive microenvironment generated by apical bud and dental mesenchyme from 7-day-old C57 mice, FDPMCs in vitro demonstrated odontogenic potential, as indicated by the morphological transformation, cell-cycle change and expression of tooth-specific markers. Under the same microenvironment, FDPMCs were incubated in vivo for 3 weeks. Coexpression of GFP and DSP proteins in the odontoblast layer was detected in the recovered implants, suggesting that GFP(+) FDPMCs can function as odontoblasts in vivo. Together, our data indicate for the first time that whisker FDPMCs from adult mice can differentiate to odontoblast-like cells.

The biological effect of dentin noncollagenous proteins (DNCPs) on the human periodontal ligament stem cells (HPDLSCs) in vitro and in vivo.

It was recognized that periodontal progenitor cells penetrate disintegrated Hertwig's epithelial root sheath, and contact with root dentin give rise to periodontium formation. Clinically, direct contact of the conditioned or denuded root surfaces with periodontal cells seems to be a prerequisite for periodontal regeneration. In this study, we investigated the biological effect of dentin noncollagenous proteins (DNCPs) on the human periodontal ligament stem cells (HPDLSCs) in vitro and in vivo. Chemical-conditioned root dentin (CCRD) was prepared by process of partly demineralization and deproteinization. Treated HPDLSCs with DNCPs showed increased proliferation and adhesion ability. Induced HPDLSCs presented several features of cementoblast differentiation, as indicated by morphologic changes, enhanced alkaline phosphatase (ALP) activity, increased matrix mineralization, and upregulated expression of mineralization-associated genes. Incubation of treated HPDLSC aggregate in vivo revealed that cementum-like tissues formed along the CCRD surface with fibrous tissue adjacent to or inserted into it, but untreated HPDLSCs cannot form similar structure. To our knowledge, this is the first study to apply active proteins derived from dentin with periodontal stem cells to construct periodontal structure, which may shed light on human periodontal tissue regeneration.

[Clinical research of rehabilitating bilateral total maxillary defects with a new improved implants and magnetic attachments bar frameworks: report of 9 cases].

PURPOSE: The purpose of this study was to research the clinical effects of a new improved implant-magnetic attachment bar framework supported the total maxillary prosthesis. METHODS: Nine patients underwent tumor resection with defect of bilateral maxilla, and after at least 1 year,4 implants was inserted into their bilateral zygomatics in every patient. A kind of new improved bar framework were fabricated with implants tightly. Based on these bar framework ,total maxillary prostheses were completed finally. RESULTS: The new improved bar framework was utilized to support the prosthesis, it was observed that the prosthesis was more stable. All patients were satisfied with mastication, speech and appearance after wearing the prosthesis. The prosthesis demonstrated a significant improvement in function and esthetics. CONCLUSIONS: It is concluded that from the practical point of view,the prosthesis with new bar framework is superior to the previous one, and its clinical prosperity is wide. But further studies are necessary to evaluate its long term effects.