Notch signaling: Its essential roles in bone and craniofacial development.

Notch is a cell-cell signaling pathway that is involved in a host of activities including development, oncogenesis, skeletal homeostasis, and much more. More specifically, recent research has demonstrated the importance of Notch signaling in osteogenic differentiation, bone healing, and in the development of the skeleton. The craniofacial skeleton is complex and understanding its development has remained an important focus in biology. In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton, skull, and face develop. We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system, and what importance it may play in the future.

The wonders of BMP9: From mesenchymal stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism to regenerative medicine.

Although bone morphogenetic proteins (BMPs) initially showed effective induction of ectopic bone growth in muscle, it has since been determined that these proteins, as members of the TGF-ß superfamily, play a diverse and critical array of biological roles. These roles include regulating skeletal and bone formation, angiogenesis, and development and homeostasis of multiple organ systems. Disruptions of the members of the TGF-ß/BMP superfamily result in severe skeletal and extra-skeletal irregularities, suggesting high therapeutic potential from understanding this family of BMP proteins. Although it was once one of the least characterized BMPs, BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo, with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs. The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants, revealing the great translational promise of BMP9. Furthermore, emerging evidence indicates that, besides its osteogenic activity, BMP9 exerts a broad range of biological functions, including stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism. This review aims to summarize our current understanding of BMP9 across biology and the body.

Association of Injury Energy Level and Neurovascular Injury Following Knee Dislocation.

OBJECTIVE: To describe the associations between mechanism of injury energy level and neurovascular injury (NVI) following knee dislocation (KD) using a large representative sample of trauma patients and to examine risk factors within these groups. DESIGN: Retrospective cohort study. SETTING: Trauma centers participating in the American College of Surgeons National Trauma Data Bank. PARTICIPANTS: Adult patients with KD without lower extremity fracture. INTERVENTION: Patients were grouped as ultra-low, low, or high-energy based on injury mechanism. Univariate/multivariate analyses assessed associations of energy level with NVI and of patient characteristics with NVI within energy-level groups. MAIN OUTCOME MEASUREMENTS: Rate of nerve and blood vessel injury. RESULTS: One hundred twenty-four patients with KD were identified; 181 sustained ultra-low-energy mechanisms, 275 low-energy, and 868 high-energy. Nerve injury occurred in 6% of ultra-low-energy injuries, 7% in low-energy, and 3% in high-energy (P = 0.03). Vessel injury occurred in 21% of ultra-low-energy injuries, 17% in low-energy, and 13% in high-energy (P = 0.01). On multivariate analyses, obesity was associated with nerve injury in the ultra-low-energy group (OR 4.9; 95% CI 1.0-24.0) but not with other energy levels. Obesity was also associated with vessel injury in the ultra-low-energy group (OR 4.0; 95% CI 1.6-9.7). Smoking, hypertension, and diabetes were not associated with NVI. CONCLUSIONS: NVI following KD is more common after lower energy-level mechanisms. Obesity is associated with NVI in lower energy-level mechanisms. Physicians should be vigilant in screening for NVI in the setting of KD even with seemingly benign mechanisms of injury, especially in patients with obesity. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Tendinopathy treatment: where is the evidence?

Tendinopathy is a common and debilitating condition that results in significant deficits in performance and prolonged time away from activity. For this reason, much effort has been placed in defining beneficial and cost-effective treatments. This review has outlined the current literature on some of the most widely used therapies for cases of tendinopathy. As such, recommendations remain limited by the evidence available. The variability in both quantity and quality of research into tendinopathy treatments makes it difficult to make definitive treatment recommendations. In general, however, a reasonable first line of treatment for tendinopathy should include a course of NSAIDs and eccentric exercise-based physical therapy. Corticosteroid injections seem to offer excellent short-term pain relief but lack long term efficacy. Alternative injections, such as PRP, have shown short-term efficacy for tendinopathy sufferers; data are lacking to support sclerosing agents and proteinase inhibitors. Operative management seems to offer some benefit in symptomatic relief but carries a higher complication rate than other treatment options and should be reserved only for patients recalcitrant to other more conservative options. Although the inability to make definitive therapeutic recommendations in some instances is discouraging, it is important to note that a lack of high-quality evidence supporting specific treatments does not necessarily imply that they are inherently ineffective. Given the growing prevalence of tendinopathy and the impact it has on the general public, it is more important now than ever to continue the search for the most effective and accessible treatment modalities.

Human growth hormone and the development of osteochondritis dissecans lesions.

No single etiology regarding the cause of osteochondritis dissecans (OCD) lesions is unanimously accepted. This report documents a novel case of multiple OCD lesions affecting the left knee and a solitary defect of the right elbow in a patient with acquired human growth hormone (hGH) deficiency and supplementation. hGH deficiency and hormone replacement may be related to the development of OCD lesions.