Correction: MMP-3 gene polymorphisms are associated with increased risk of osteoarthritis in Chinese men.

[This corrects the article DOI: 10.18632/oncotarget.18493.].

MMP-3 gene polymorphisms are associated with increased risk of osteoarthritis in Chinese men.

Osteoarthritis (OA) is the most common late-onset degenerative joint disease., It is characterized by progressive degradation of articular cartilage. We investigated the association between OA occurrence and single nucleotide polymorphisms (SNPs) in the matrix metalloproteinase-3 (MMP-3) gene involved in the breakdown of extra-cellular matrix proteins. The study included 100 male OA patients and 197 healthy men from the north area of China. Eight MMP-3 SNPs were genotyped. Odds ratios (ORs) with 95% confidence intervals (95%CIs) and multivariate logistic regression analysis were used to assess the association. Multivariate logistic regression analysis was used to identify SNPs that correlated with OA susceptibility. We found that rs639752 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.00, 95% CI: 1.03-3.88, P = 0.037); rs520540 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.00, 95% CI: 1.03-3.88, P = 0.037); rs602128 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.01, 95% CI: 1.03-3.89, P = 0.037); and rs679620 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.04, 95% CI: 1.05-3.96, P = 0.033) were associated with the increased risk of OA. Our results suggest that these SNPs may contribute to OA development, and could serve as molecular markers of OA susceptibility.

TIMP-2 SNPs rs7342880 and rs4789936 are linked to risk of knee osteoarthritis in the Chinese Han Population.

This study aimed to investigate whether functional polymorphisms in the tissue inhibitors of metalloproteinase-2 (TIMP-2) gene are associated with susceptibility to knee osteoarthritis (OA) in the Chinese Han population. Six TIMP-2 single nucleotide polymorphisms (SNPs) were assayed using MassARRAY in 300 patients clinically and radiographically diagnosed with knee OA and in 428 controls. Allelic and genotypic frequencies were compared between groups. Logistic regression adjusting for age and gender was used to estimate risk associations between specific genotypes and knee OA by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that allele "A" in rs7342880 was significantly associated with increased risk of knee OA (OR = 1.44, 95%CI = 1.09-1.91, p = 0.035). In addition, in the over-dominant model, rs4789936 correlated with reduced risk of knee OA, adjusting for age and gender (OR = 0.69, 95%CI = 0.49-0.98, p = 0.036). Finally, rs7342880 correlated with increased risk of knee OA in females. This study provides evidence that TIMP-2 is a knee OA susceptibility gene in the Chinese population and a potential diagnostic and preventive marker for the disease.

Hypoxia promotes AMP-activated protein kinase (AMPK) and induces apoptosis in mouse osteoblasts.

The hypoxic environment around the fracture site develops post the blood flow disruption and leads to osteoblast cell death and further impairs fracture healing. Hypoxia usually leads to the mitochondrial dysfunction and then results in apoptotic cell death. AMPK is ubiquitously expressed and functions as an intracellular fuel sensor by maintaining energy balance, as is potentially activated by hypoxia, ischemia, and ROS, however, the regulatory role of AMPK in hypoxia-induced apoptosis in osteoblasts and in the fracture healing has not been identified. In present study, we firstly determined the apoptosis induction by hypoxia in mouse osteoblastic MC3T3-E1 cells via examining the apoptotic cells and the activation of apoptosis-related molecules, then investigated the activation of AMPK signaling by hypoxia via analyzing the phosphorylation of AMPKα and ACC1, finally we explored the association of the AMPK activation with the hypoxia-induced apoptosis using loss-of-function strategy. Results demonstrated that hypoxia induced apoptosis in MC3T3-E1 cells and activated the AMPK signaling. And the knockdown of AMPK via chemical treatment or RNA interfering significantly decreased the hypoxia-induced apoptosis in MC3T3-E1 cells. Taken together, present study unveiled the regulatory role of AMPK signaling in the hypoxia-induced osteoblast apoptosis.

Improved Achilles tendon healing by early mechanical loading in a rabbit model.

OBJECTIVE: To investigate the structure and the attachment strength of a healing tendon-bone interface and the role of mechanical loading in tendon healing. METHODS: Sixty rabbits underwent unilateral detachment and repair of the Achilles tendon. Thirty animals were immobilized (Group A), and the others wereallowed loadingimmediately postoperatively (Group B). Animals were sacrificed at 4 weeks and evaluated for histological and biomechanical testing. Statistical analysis was performed with an independent t test with significance set at P = 0.05. RESULTS: The ultimate stress was greater in group B (4.598 ± 1.321 N/mm(2)) compared with the control group (3.388 ± 0.994 N/mm(2)) (P < 0.05). Similarly, a more organized tendon-to-bone interface with a larger area of chondrocytes was found in group B (P < 0.05). CONCLUSION: Mechanical loading improves the structure and the attachment strength of the healing tendon-to-bone interface.