Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis.

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 µg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.

Genes relevant with osteoarthritis by comparison gene expression profiles of synovial membrane of osteoarthritis patients at different stages.

BACKGROUND: This study aimed to identify biological markers about osteoarthritis (OA) which is a polygenic disease by investigating the gene expression profiles of the synovium samples from early-stage and end-stage OA patients for the diagnosis and treatment of OA. METHODS: The gene expression profile of GSE32317 was downloaded from Gene Expression Omnibus (GEO) database, including 10 samples from early-stage OA patients and 9 samples from end-stage OA patients. The differentially expressed genes (DEGs) were identified by Significance Analysis of Microarrays. The co-expression network of DEGs was constructed by Pearson correlation test. Then, modules in the constructed co-expression network were selected by MCODE Plugin. What's more, EASE (Expression Analysis Systematic Explorer) was used to define the significant functions and pathways in the identified modules. RESULTS: Total 419 DEGs were identified, among which 112 were up-regulated and 307 down-regulated. We selected 7 statistically significant modules with gene number above 10 and phenotypic correlation test of modules showed that all the modules had significant correlation with OA (p < 0.05). The genes of module 1, module 2 and module 7 were significantly related to immune system functions, protein glycosylation functions, bone, chondrocytes and cartilage functions, respectively. The most significant pathway in module 3 and module 5 was Wnt signal pathway, and in module 4 was Toll-like receptor signal pathway. CONCLUSIONS: DEGs related to immune response, cartilage development, protein glycosylation, muscle development, and DEGs participated in the Wnt signaling pathway and Toll-like receptor (TLR) signaling pathway might be the potential target genes for the OA treatment.

Comparative genome-wide gene expression analysis of rheumatoid arthritis and osteoarthritis.

Both rheumatoid arthritis (RA) and osteoarthritis (OA) are complex diseases. Studies and treatment of RA and OA have mainly focused on individual factors. However, there is still no clear understanding of their causes and adequate treatment alternatives are still being sought. We applied gene set-enrichment analysis to microarray datasets of RA and OA to look for regulatory mechanisms. We found 32 highly significant pathways, including 18 downregulated and 14 upregulated pathways associated with RA. We also identified 18 highly significant pathways, including 7 downregulated and 11 up-regulated pathways associated with OA. Several such pathways were found in both RA and OA, including an upregulated PPAR signaling pathway and downregulated leukocyte transendothelial migration. Regulatory mechanisms in RA seem to be more complex than in OA. This information could be useful for diagnosis and treatment of these two diseases.

[Study on sijunzi decoction in rectifying digestive disorder in mice].

OBJECTIVE: To observe the Sijunzi Decoction in rectifying the digestive disorder. METHODS: Sijunzi decoction (SJZD) was chosen to treat digestive dysfunction in mice. The model was induced by Xiaochengqi decoction and semi-starvation. The effects on the absorptive function of the small intestine, body weight, autonomous activity levels, oxidative phosphorylation of hepatic mitochondrion, respiratory control rate (RCR) and cells energy charge were observed in vivo. RESULTS: The group given Xiaochengqi decoction had lower absorption, decreased body weight, and lower autonomous activity levels, and their hepatic mitochondrion RCR and cell energy charge were also lower than those of the control group. The figures for the group given SJZD all showed improvement, especially the group given the larger dose of SJZD. CONCLUSION: SJZD could correct Deficiency of the Spleen and Stomach which to some extent is caused by digestive dysfunction. So it is considered that the Spleen's function of transportation and transformation includes two meanings: external transportation and transformation--the digestive and absorptive function of the small intestine, and internal transportation and transformation--the liver's conversion of nutrients and generate energy (ATP).

Study of gastric and gallbladder kinetics with real-time ultrasonography in cases of functional dyspepsia.

Gastric and gallbladder emptying in 113 patients with functional dyspepsia (FD) were evaluated by real-time ultrasonography (RUS) after a liquid-fat meal by the patients, and compared with 15 healthy volunteers. The results showed that in FD group 69 patients (61.06%) had delayed gastric emptying, and 28 patients (24.77%) had gallbladder hypokinesia. Among them both delayed gastric emptying and gallbladder hypokinesia were found in 11 patients (9.7%), 44 patients (38.93%) had normal gastric emptying and 85 patients (75.22%) had normal gallbladder emptying.