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Statement of problem The internal connection is a widely used implant-abutment connection. However, a meta-analysis comparing the internal tapered and nontapered connection systems is lacking. Purpose The purpose of this systematic review and meta-analysis was to assess whether the internal tapered connection performs better than the internal nontapered connection in terms of implant survival, marginal bone loss, probing depths, and complications. Material and methods The following specific question was formulated based on the Population, Intervention, Control, and Outcome (PICO) model: Do patients receiving internal tapered connection implants show better prognosis than those receiving the internal nontapered connection in terms of implant survival, marginal bone loss, probing depths, and complications? An electronic systematic literature search was conducted in the Cochrane Library databases, MEDLINE (PubMed), and Embase for relevant studies published in English without time restrictions. A manual search was also conducted. In vivo randomized controlled trials (RCTs) and prospective cohort studies were included. Results A total of 592 studies were collected from the electronic and manual searches. After independent screening by 2 reviewers, 5 RCTs and 2 prospective cohort studies were included. No significant difference was observed in implant survival rates (P=.47; RR: 1.01; 95% CI: 0.98, 1.05). Regarding marginal bone loss, the internal tapered connection presented better results than the nontapered connection (P=.003; MD: −0.43 mm; 95% CI: −0.73, −0.14). The internal tapered connection also exhibited lower probing depths than the nontapered one (P=.002; MD: −0.24 mm; 95% CI: −0.39, −0.09). No significant difference was observed in complication rates (P=.47; RR: 1.21; 95% CI: 0.72, 2.04). Conclusions Within the limitations of this systematic review and meta-analysis, the internal tapered connection and nontapered connection were comparable in terms of implant survival rates and complication rates. In contrast to the internal nontapered connection, marginal bone loss and probing depths in the tapered connection were significantly lower.

N6-methyladenosine (m6A) methylation is one of the most common internal modifications in eukaryotic messenger RNA occurring on N6 nitrogen of adenosine. However, the roles of m6A in temporomandibular joint osteoarthritis (TMJ OA) are still elusive. Here, we investigate the function and mechanism of methyltransferase-like 3 (Mettl3) in chondrocytes in inflammation. We found that the expression of Mettl3 decreased both in vivo TMJ OA mice and in vitro inflammatory stimulation. Functionally, loss and gain studies illustrated that Mettl3 inhibited the apoptosis and autophagy of chondrocytes induced by TNF-α stimulation in vitro. Mettl3 inhibitor, S-adenosylhomocysteine (SAH) promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced TMJ OA mice in vivo. Mechanistically, the bioinformatics analysis, m6A-RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) were used to identify that Bcl2 mRNA was the downstream target of Mettl3 for m6A modification. Furthermore, the results revealed that Yth m6A RNA binding protein 1 (Ythdf1) mediated the stability of Bcl2 mRNA catalyzed by Mettl3. Co-immunoprecipitation (Co-IP) showed that Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-α stimulation. In conclusion, our findings identify that Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for TMJ OA.

Cellular senescence is the inability of cells to proliferate, which has both beneficial and detrimental effects on tissue development and homeostasis. Chronic accumulation of senescent cells is associated with age-related disease, including osteoarthritis, a common joint disease responsible for joint pain and disability in older adults. The pathology of this disease includes loss of cartilage, synovium inflammation, and subchondral bone remodeling. Senescent cells are present in the cartilage of people with advanced osteoarthritis, but the link between cellular senescence and this disease is unclear. In this review, we summarize current evidence for the role of cellular senescence of different cell types in the onset and progression of osteoarthritis. We focus on the underlying mechanisms of senescence in chondrocytes, which maintain the cartilage in joints, and review the role of the Forkhead family of transcription factors, which are involved in cartilage maintenance and osteoarthritis. Finally, we discuss the potential therapeutic value and implications of targeting senescent cells using senolytic agents or immune therapies, targeting the senescence-associated secretory phenotype of these cells using senomorphic agents, and renewing the plasticity of stem cells and chondrocytes. Our review highlights current gaps in understanding of the mechanism of senescence that may, when addressed, provided new options for modifying and treating disease in osteoarthritis.

Background: Osteoclastogenesis is a key process in osteolytic bone metastasis (BM). Previous studies indicated that miRNAs could regulate cancer progression and osteoclastogenesis. Our purpose was to investigate the roles of lung cancer cells-derived circulating miR-21 on osteoclastogenesis and its clinical significance in BM patients. Methods: The difference of miRNA expression in two lung cancer cell lines SBC-5 (with characteristic BM ability) and SBC-3 (without BM ability) were analyzed. Circulating miR-21 levels of lung cancer patients with or without BM were compared. The effects of conditioned media from lung cancer cell lines or patients' plasma with different miR-21 levels on osteoclastogenesis were investigated. The diagnostic performance of circulating miR-21 in BM patients was evaluated. Findings: We found that miR-21 expression was specifically higher in SBC-5 than that in SBC-3 cells. The supernatants of SBC-5 cells with higher level miR-21 promoted osteoclastogenesis. Moreover, we demonstrated that the circulating miR-21 level was significantly higher in BM patients than that in non-BM patients. The plasma from BM patients with higher level miR-21 could also promot osteoclastogenesis. Mechanistically, lung cancer cells-derived circulating miR-21 could be transferred into osteoclast precursor cells and promot osteoclastogenesis probably by inhibiting PTEN (Phosphatase and tensin homologue). Finally, we indecated that circulating miR-21 had a potential for the diagnosis of BM. Interpretation: Our findings suggested circulating miR-21 played important roles in BM of lung cancer and may service as a biomarker to diagnose BM in lung cancer patients. Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 81572639, 81770875, 81370969), Department of Science and Technology of Sichuan Province (2018SZ0142), and Sichuan University (2018SCUH0093). Declaration of Interest: No potential conflicts of interest were disclosed. Ethical Approval: The study was approved by the hospital research ethics committee of West China Hospital of Sichuan University and conducted in accordance with the International Ethical Guidelines for Biomedical Research Involving Human Subjects. All patients included in this study had signed the informed consent form.

Fibroblast growth factor-23 (FGF23) is a circulating factor that plays critical roles in phosphate and vitamin D metabolism. The goal of our studies was to dissect the pathways directing the vitamin D-phosphate-FGF23 homeostatic axis. To test the role of diet in the regulation of Fgf23, wild-type (WT) mice were fed either a standard (0.44% phosphorus) or a low-phosphate (0.02%) diet. WT mice on standard diet had a serum phosphate of 9.5 +/- 0.3 mg/dl and an Fgf23 concentration of 99.0 +/- 10.6 pg/ml; mice on the low-phosphate diet had a phosphate of 5.0 +/- 0.2 mg/dl (P0.01) and an Fgf23 of 10.6 +/- 3.7 pg/ml (P0.01). To genetically separate the effects of phosphate and vitamin D on Fgf23, we examined vitamin D receptor null (VDR(-/-)) mice, which are hypocalcemic and hypophosphatemic secondary to hyperparathyroidism. On standard diets, WT and VDR(+/-) mice had Fgf23 levels of 106.0 +/- 30.7 and 90.6 +/- 17.3 pg/ml, respectively, whereas Fgf23 was undetectable in the VDR(-/-). Animals were then placed on a diet that normalizes serum calcium and phosphorus. This 'rescue' increased Fgf23 in WT to 192.3 +/- 32.5 pg/ml and in VDR(+/-) to 388.2 +/- 89.6pg/ml, and importantly, in VDR(-/-) to 476.9 +/- 60.1 pg/ml (P0.01 vs. WT). In addition, renal vitamin D 1-alpha hydroxylase (1alpha-OHase) mRNA levels were corrected to WT levels in the VDR(-/-) mice. In summary, Fgf23 is suppressed in diet-induced hypophosphatemia and in hypophosphatemia associated with secondary hyperparathyroidism. Normalization of serum phosphate by diet in VDR(-/-) mice increases Fgf23. Thus, our results demonstrate that Fgf23 is independently regulated by phosphate and by vitamin D.

SHARPIN is a novel protein thought to interact with SHANK family and is widely expressed in multiple tissues/cells, including osteoblasts and osteoclasts. Loss-of-function of Sharpin develops the chronic proliferative dermatitis mutation (CPDM) in mice as well as a severe inflammation in other organs. The actual function of SHARPIN is poorly understood. Our aim was to determine the functional roles of SHARPIN in bone metabolism by using CPDM mice. The skeletal phenotypes were determined by peripheral quantitative computed tomography, micro-computed tomography, and quantitative real-time RT-PCR, the cellular functions of osteoblasts and osteoclasts were investigated by ex vivo cell culture. Compared to wild-type controls, CPDM mice demonstrated significantly lower total and cortical bone mineral content and bone mineral density, trabecular and cortical bone volume, and trabecular number. The mRNA expression of Runx2, osterix, type I collagen, and osteocalcin was significantly lower in the bone from CPDM mice. Osteoclasts and osteoblasts from CPDM mice were functionally defective. Our result suggests that SHARPIN plays important regulating roles in bone metabolism. These functional roles may either come from systemic chronic inflammatory or directly signaling pathway within bone cells.