Efficient in vitro delivery of Noggin siRNA enhances osteoblastogenesis.

Several types of serious bone defects would not heal without invasive clinical intervention. One approach to such defects is to enhance the capacity of bone-formation cells. Exogenous bone morphogenetic proteins (BMP) have been utilized to positively regulate matrix mineralization and osteoblastogenesis, however, numerous adverse effects are associated with this approach. Noggin, a potent antagonist of BMPs, is an ideal candidate to target and decrease the need for supraphysiological doses of BMPs. In the current research we report a novel siRNA-mediated gene knock-down strategy to down-regulate Noggin. We utilized a lipid nanoparticle (LNP) delivery strategy in pre-osteoblastic rat cells. In vitro LNP-siRNA treatment caused inconsequential cell toxicity and transfection was achieved in over 85% of cells. Noggin siRNA treatment successfully down-regulated cellular Noggin protein levels and enhanced BMP signal activity which in turn resulted in significantly increased osteoblast differentiation and extracellular matrix mineralization evidenced by histological assessments. Gene expression analysis showed that targeting Noggin specifically in bone cells would not lead to a compensatory effect from other BMP negative regulators such as Gremlin and Chordin. The results from this study support the notion that novel therapeutics targeting Noggin have the clinically relevant potential to enhance bone formation without the need for toxic doses of exogenous BMPs. Such treatments will undeniably provide safe and economical treatments for individuals whose poor bone repair results in permanent morbidity and disability.

Self-inflicted non-healing genital ulcer: a rare form of factitious disorder.

Dermatitis artefacta is a factitious dermatological disorder with many forms of presentation that may occur on any part of the body. A diagnosis of dermatitis artefacta is often reached after rigorous and repeated investigations. Here we present the case of a 49-year-old single man complaining of a 4- month history of ulceration on the dorsal surface of the glans penis. In view of the unusual appearance of the lesion and the negative findings from clinical investigations, a diagnosis of dermatitis artefacta was made and the patient was referred for psychiatric evaluation. He was started on 20 mg/day of citalopram and titrated up to 40 mg/day by the 4th week, leading to complete remission in the following weeks. Thus, although rare, artefactual dermatitis should be considered in the differential diagnosis of unusual penile lesions.