Molecular and Cellular Effects of Chemical Chaperone-TUDCA on ER-Stressed NHAC-kn Human Articular Chondrocytes Cultured in Normoxic and Hypoxic Conditions.

Osteoarthritis (OA) is considered one of the most common arthritic diseases characterized by progressive degradation and abnormal remodeling of articular cartilage. Potential therapeutics for OA aim at restoring proper chondrocyte functioning and inhibiting apoptosis. Previous studies have demonstrated that tauroursodeoxycholic acid (TUDCA) showed anti-inflammatory and anti-apoptotic activity in many models of various diseases, acting mainly via alleviation of endoplasmic reticulum (ER) stress. However, little is known about cytoprotective effects of TUDCA on chondrocyte cells. The present study was designed to evaluate potential effects of TUDCA on interleukin-1ß (IL-1ß) and tunicamycin (TNC)-stimulated NHAC-kn chondrocytes cultured in normoxic and hypoxic conditions. Our results showed that TUDCA alleviated ER stress in TNC-treated chondrocytes, as demonstrated by reduced CHOP expression; however, it was not effective enough to prevent apoptosis of NHAC-kn cells in either normoxia nor hypoxia. However, co-treatment with TUDCA alleviated inflammatory response induced by IL-1ß, as shown by down regulation of Il-1ß, Il-6, Il-8 and Cox2, and increased the expression of antioxidant enzyme Sod2. Additionally, TUDCA enhanced Col IIα expression in IL-1ß- and TNC-stimulated cells, but only in normoxic conditions. Altogether, these results suggest that although TUDCA may display chondoprotective potential in ER-stressed cells, further analyses are still necessary to fully confirm its possible recommendation as potential candidate in OA therapy.

The Challenges of Monoaxial Bone Transport in Orthopedics and Traumatology.

BACKGROUND: Bone defects represent the main challenging problem for the orthopedic surgeon and, consequently, they increase the duration of hospitalization, risk of complications and health expenditures. The aim of our observational, descriptive and retrospective study is to evaluate the outcomes of patients treated with a mo-nolateral external fixator for bone defects greater than 3 cm. MATERIAL AND METHODS: Between January 2003 and January 2013, 21 patients were treated at our center by bone transfer with a monolateral external fixator. The main etiologies were trauma in 17 cases (80.9%) and tumors in 4 cases (19.1%). Mean follow-up was 5 years for non-union and 3 years for tumors. Our clinical evaluation was based on ASAMI (Association for the Study ad Application of the Methods of Ilizarov) scores during this follow-up period. RESULTS: The functional outcomes, based on ASAMI scores, were excellent in 12 cases, good in 7 and poor in 2. CONCLUSION: 1. A review of the literature related to our experience shows that bone transport is an effective tech-nique to repair loss of bone in the lower limbs. The use of a system of external fixation enables corrective actions throughout the treatment that can be in-dividualized on a case-by-case basis. In our experience, the LRS fixator (Orthofix) is a sta-ble, easy-to-use and very handy device. 2. In situations where soft tissue reconstruction procedures are needed, the size and shape of the splint should be such as not to constitute an obstacle. Fur-thermore, the use of pins rather than transfixation wires eliminates the risk of neuro / vascu-lar injury such as may occur during the application of a circular fixator. 3. The analysis of the cases presented here indicates that where possible the technique of bone transport produces good results and can often salvage the limb. Amputation should be reserved only for cases where the general and / or local preoperative status indicate that the surgeon can expect a poor result or when the compliance of the patient is determined to be inadequate.