Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1 could bind with NRF2 in chondrocytes, which subsequently suppresses the transcription of SIRT3 in vitro. In addition, SIRT3 reduction could promote the acetylation of FOXO3a and result in mitochondrial dysfunction, which finally contributes to the degradation of chondrocytes. To conclude, this work revealed the critical role and underlying mechanism of senescent FLSs-derived CRTAC1 in OA progression, which provided a potential strategy for the OA therapy.

Objective To investigate the differences in blood pressure phenotypes,renal pathological changes,and related pathogenic pathways in genetically diverse hypertensive mice obtained from 13 strains.Methods The genotypes of Cckbr+/+,Cckbr+/-and Cckbr-/-were obtained by hybridization of 13 strains of genetically diverse mice with Cckbr-/-mice.Blood pressure was measured with a noninvasive blood pressure analysis system(BP-2000).The expression of CCKBR protein in mouse kidney tissue was detected by Western Blot,and the pathological changes in mouse kidney tissue were detected by hematoxylin-eosin(HE)staining and immunohistochemistry(IHC).The pathogenic pathways related to essential hypertension were screened by RNA sequencing.Results In three specific mouse strains(A/J,LOT,and FIM),the systolic blood pressure(SBP)was significantly different between the Cckbr-/-and Cckbr+/+groups.HE staining and IHC showed that hypertension caused a certain degree of renal injury in the mice.Gene Ontology(GO)and pathway enrichment analysis showed that differentially expressed genes were enriched in metabolic processes and circadian rhythm regulation.Conclusions Genetically diverse mice can effectively simulate the genetic background of the population and provide a new resource for studying the pathogenic genes related to essential hypertension.

Objective To investigate the relationship of serum adiponectin (APN) gene promoter region single nucleotide polymorphism (SNP) frequency and type 2 diabetes mellitus (T2DM).Methods 120 cases of T2DM were divided into Yin Deficiency Syndromes(n=42), Yin hot (n=38), yin and yang (n=40) and 50 cases of normal volunteers were select as the control group. The diponectin gene (aPM1) promoter polymorphisms of each group were detected with polymerase chain reaction amplification (PCR).Results Serum APN Yin hot levels in patients with T2DM (6.98 ± 1.23 μg/ml) were lower than Qi and yin (2.55 ± 0.78 μg/ml) and yang group (3.48 ± 0.22 μg/ml) (P<0.05), and TG, LDL-C, TC (4.48 ± 0.87 mmol/L, 4.98 ± 0.42 mmol/L, 5.36 ± 0.79 mmol/L) were higher than Qi and yin (3.25 ± 0.75 mmol/L, 4.02 ± 0.69 mmol/L, 3.12 ± 0.52 mmol/L) and yang group (3.18 ± 0.69 mmol/L, 4.09 ± 0.71 mmol/L, 3.22 ± 0.78 mmol/L)(P<0.05). Yin hot type aPM1-11377G/C genotype of the GG genotype was significantly higher than the proportion of Qi and yin and yang group (P<0.05), while the yin and yang and yin and yang group aPM1-11377G/C genotype the proportion was higher in GG genotype (P<0.05). GG genotype was significantly lower than serum APN type CG and CC genotype (P<0.05), whereas no significantdifference in other indexes (P>0.05).Conclusion T2DM patients Yin hot type inherent relationship with aPM1-11377G/C polymorphism, aPM1-11377G/C polymorphism may reflect R2DM Disease Syndromes typing a certain extent, and by influence insulin resistance in patients with arterial plaque and serum APN levels, thereby affecting T2DM disease occurrence and progression.