Lunasin abrogates the expression of matrix metalloproteinases and reduction of type II collagen.

Impairment of type II collagen caused by MMPs in response to overproduction of IL-1ß is an important step in the pathological progression of osteoarthritis (OA). Lunasin, a well-known peptide present in the soybean, has displayed a positive impact on numerous physiological functions. Little information in the effects of lunasin on cartilage degradation has been sought in clinical research before. Here, we report that lunasin suppressed the increase in MMP-3 and MMP-13 caused by IL-1ß. In addition, we found that lunasin could prevent the decrease in TIMP-1 and TIMP-2 expressions caused by IL-1ß. Notably, lunasin suppressed reduction of type II collagen, the basis for articular cartilage. Lunasin also attenuated activation of the JAK2/STAT1/IRF-1 pathway. These effects of lunasin suggest that it might become a promising therapeutic agent for chondro-protective therapy.

Regulatory effect of miR-421 on humeral fracture and heterotopic ossification in elderly patients.

The present study aimed to investigate the role of miR-421 and bone morphogenetic protein-2 (BMP-2) in the bone tissues and blood of elderly patients with humeral fractures and heterotopic ossification. A total of 38 patients with humeral fractures, including 16 patients who received surgery within 1-7 days of fracture and 22 patients who received surgery within 8-14 days of fracture, were enrolled. An additional 18 patients who had heterotopic ossification and 26 patients who had humeral fracture and not heterotopic ossification were also included. Bone tissues and blood were collected. Reverse transcription-quantitative polymerase chain reaction was performed to determine the miR-421 and BMP-2 mRNA expression levels in the samples. Western blotting and ELISA were performed to detect BMP-2 protein levels in bone tissues and blood, respectively. Dual-luciferase reporter assays were performed to verify whether BMP-2 is the direct target gene of miR-421. Compared with the patients who received surgery 1-7 days after fracture, the patients who accepted the surgery 8-14 days after fracture had significantly increased levels of BMP-2 mRNA and protein in their bone tissues and blood (P<0.05). Contrastingly, the expression level of miR-421 decreased in the samples from patients who accepted the surgery 8-14 days after fracture compared with the level in those who received surgery 1-7 days after fracture (P<0.05). Compared with the patients without heterotopic ossification, the patients with heterotopic ossification had increased BMP-2 mRNA and protein expression levels in their bone tissues and blood, whereas the expression of miR-421 was significantly decreased (P<0.05). The dual-luciferase reporter assay demonstrated that BMP-2 was the direct target gene of miR-421. The upregulation of BMP-2 may be associated with the downregulation of miR-421. miR-421 may regulate the recovery of humeral fracture and heterotopic ossification through BMP-2. The results of the present study may provide a theoretical basis for the diagnosis and treatment of humeral fracture and heterotopic ossification.

Plasma Brain Natriuretic Peptide, Endothelin-1, and Matrix Metalloproteinase 9 Expression and Significance in Type 2 Diabetes Mellitus Patients with Ischemic Heart Disease.

BACKGROUND: Type 2 diabetes (DMT2) combined with ischemic heart disease (IHD) promotes the occurrence and development of coronary atherosclerosis. We aimed to provide a theoretical basis for improving patient prognosis through analyzing expression of plasma brain natriuretic peptide (BNP), endothelin-1 (ET 1), and matrix metalloproteinase 9 (MMP-9). MATERIAL AND METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect BNP, ET-1, and MMP-9 levels in 50 patients with DMT2 only (group A), 47 patients with IHD only (group B), 43 patients with comorbid (both) IHD and DMT2 (group C), and 50 health controls (group D). Group C was further divided into single-branch lesion group, double-branch lesions group, and triple-branch lesion group according to coronary angiography, or cardiac function grade II, III, and IV group according to cardiac function, and their BNP, ET-1, and MMP-9 levels were compared. RESULTS: Compared with group D, TG, diastolic, and systolic blood pressure were all significantly elevated in groups A, B, and C. Group C exhibited obviously higher glycosylated hemoglobin than group A. Gensini score in group C was markedly higher than in group B. Compared with group D, BNP, ET-1, and MMP-9 levels were all increased in groups A, B, and C. Group C showed higher levels of BNP, ET-1, and MMP-9 than group A and B. BNP, ET-1, and MMP-9 levels in the triple-branch lesions group were higher than in the single-branch lesions group and double-branch lesions group. The cardiac function grade IV group presented higher levels of BNP, ET-1, and MMP-9 than did the grade II and III groups. BNP, ET-1, and MMP-9 showed a positive correlation to each other. CONCLUSIONS: BNP, ET-1, and MMP-9 may participate in the occurrence and development of comorbid DMT2 and IHD. They are important objective indicators for evaluating severity and prognosis of patients with comorbid DMA2 and IHD.