ObjectivesIn this study, we aim to determine the effect of metformin on osteoarthritis (OA) development and progression.MethodsDestabilisation of the medial meniscus (DMM) surgery was performed in 10-week-old wild type and AMP-activated protein kinase (AMPK)α1 knockout (KO) mice. Metformin (4 mg/day in drinking water) was given, commencing either 2 weeks before or 2 weeks after DMM surgery. Mice were sacrificed 6 and 12 weeks after DMM surgery. OA phenotype was analysed by micro-computerised tomography (μCT), histology and pain-related behaviour tests. AMPKα1 (catalytic alpha subunit of AMPK) expression was examined by immunohistochemistry and immunofluorescence analyses. The OA phenotype was also determined by μCT and MRI in non-human primates.ResultsMetformin upregulated phosphorylated and total AMPK expression in articular cartilage tissue. Mild and more severe cartilage degeneration was observed at 6 and 12 weeks after DMM surgery, evidenced by markedly increased Osteoarthritis Research Society International scores, as well as reduced cartilage areas. The administration of metformin, commencing either before or after DMM surgery, caused significant reduction in cartilage degradation. Prominent synovial hyperplasia and osteophyte formation were observed at both 6 and 12 weeks after DMM surgery; these were significantly inhibited by treatment with metformin either before or after DMM surgery. The protective effects of metformin on OA development were not observed in AMPKα1 KO mice, suggesting that the chondroprotective effect of metformin is mediated by AMPK signalling. In addition, we demonstrated that treatment with metformin could also protect from OA progression in a partial medial meniscectomy animal model in non-human primates.ConclusionsThe present study suggests that metformin, administered shortly after joint injury, can limit OA development and progression in injury-induced OA animal models.

Study design: A systematic review. Background: The number of traumatic spinal cord injury (TSCI) reports grows annually, especially in China and Korea. The epidemiological characteristics of TSCI in Asia differ from those in other countries. Thus, we compiled epidemiological factors from Asia to compare with those from other countries. Method: We searched articles published in any language between January 1980 to December 2011 using the terms "spinal cord injury", "traumatic spinal cord injury", "epidemiology", and "Asia". The articles were reviewed for information regarding TSCI incidence, total cases, case criteria, case source, causes of injury, male/female ratio, mean age, prospective or retrospective, neurological level of injury, extent of injury, and America Spinal Injury Association Impairment Scale (AIS)/grade. Results: Epidemiological data were extracted from 39 reports in the published literature that met the inclusion criteria. Only two studies reported prevalence rates. Incidence rates ranged from 12.06 to 61.6 per million. The average age ranged from 26.8 to 56.6 years old. Men were at higher risk than women. Motor vehicle collisions (MVCs) and falls were the main causes of TSCI. However, several countries reported war wounds as the major cause. The neurological level and extent of injury were mixed, and most patients were categorized as AIS/Frankel grade A. Conclusion: TSCI is an important public health problem and a major cause of paralysis. We must understand the epidemiology to implement appropriate preventative measures. Asian epidemiology is different from that in other regions, so intervention measures must be established according to population-specific characteristics.

The results of this study are in accordance with that of most other developing countries; falls and motor vehicle collisions were the two leading causes, but the mean age was older. Percentage of the aged with traumatic spinal cord injury was increasing. The low-falls group tended to expand over this period. All these data indicated that the preventive programs should focus on the traffic accidents and falls, and more attention should be paid to the aged for the vulnerability to low fall.

Spinal cord injury (SCI) usually results in a large range of sensorimotor and autonomic nerve injury and remains a serious public health problem worldwide. SCI affects approximately 273 000 people in the United States, and there are some 12 000 new cases each year. 1-3 Therefore, SCI brings severe economy burdens and psychological pressure to patients. However, there are currently no effective therapies for SCI clinically, and an effective treatment is awaited. 4-6 This is due mainly to the molecular mechanisms of SCI remain elusive. The pathological process of SCI is known as a complex process, which can be classified into two phases: Primary injury is the direct mechanical damage of spinal cord tissue and includes demyelination and necrosis of neurons and axons; and the secondary injury is composed of a variety of pathophysiologic mechanisms, including local haemorrhage, ischaemia, oedema, ionic imbalance, free radical stress and inflammatory responses. 7,8 This complex pathological process of SCI may explain the difficulty in finding a suitable and effective therapy. Therefore, understanding the molecular mechanisms of SCI is critical for the development of therapeutic strategies. Cell death is known as the final stage of cells and it can be resulted from cytotoxicity from exogenous or endogenous substances. 9 In 1842, cell death was first posed by Carl Vogt, and lots of molecules are considered to be involved in this irreversible process to support the maintenance of cellular homeostasis. 10 Cell death was initially divided into two types, necrosis and apoptosis. 11 Necrosis is considered as a passive and accidental cell death, which can be resulted from environmental perturbations and the large amounts

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