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The NF1 tumor suppressor gene encodes a GTPase-activating protein called neurofibromin that negatively regulates Ras signaling. Mutations in NF1 cause neurofibromatosis type 1 (NF1). The development of neurofibromas, which are complex tumors composed of multiple cell types, is a hallmark of NF1. Somatic inactivation of murine Nf1 in Schwann cells is necessary, but not sufficient, to initiate neurofibroma formation. Neurofibromas occur with high penetrance in mice in which Nf1 is ablated in Schwann cells in the context of a heterozygous mutant (Nf1 +/-) microenvironment. Mast cells infiltrate neurofibromas, where they secrete proteins that can remodel the ECM and initiate angiogenesis. Thus, identification of mechanisms responsible for mast cell migration to tumor microenvironments is important for understanding tumorigenesis and for designing potential therapies. Here, we show that homozygous Nf1 mutant (Nf1 -/-) Schwann cells secrete Kit ligand (KitL), which stimulates mast cell migration, and that Nf1 +/-mast cells are hypermotile in response to KitL. Furthermore, we link hyperactivation of the Ras-class I A -PI3K-Rac2 pathway to increased Nf1 +/-mast cell migration. Thus, these studies identify a novel interaction between Nf1 -/-Schwann cells and Nf1 +/-mast cells that is likely to be important in neurofibroma formation.

Diseases involving the articular cartilage are one of the leading causes of physical impairment among the adult population. While surgical technique and advancement have allowed us effective means at treating these diseases, this is not without significant risk and morbidity. With a very solid safety profile, viscosupplementation with hyaluronic acid (HA) derivatives has become an excellent modality for treating diseased articular cartilage. Recent literature supports the use of HA not only in the management of the pain associated with osteoarthritis but also as a disease-modifying agent as well. Further studies have started to define exciting new roles for viscosupplementation in the treatment for acute injuries to the joint microenvironment.

Object The current standard of care for symptomatic chronic spondylolysis (SP) is a one-level posterior spinal fusion for defects at L-5 or direct pars repair (motion segment sparing) for more rostral SP in younger patients and if no disc degeneration or listhesis is present. Since many patients with SP undergoing operative repair are young, a procedure with the lowest biomechanical profile is desirable, and direct pars repair is recommended. The authors here explore the limits of direct pars repair. Methods A retrospective review of all patients who underwent direct repair of SP between 2002 and 2009 was performed. Data were analyzed for predictors of symptom relief and radiographic fusion failure. Results Of 49 patients, only 7 required a reoperation to treat clinical symptoms, and 6 of them were female (p = 0.049). In all cases of treatment failure, the patient had bilateral L-5 SP. Patients with a slip percentage as high as 30% experienced radiographic fusion and symptom relief. Disc degeneration (measured using the Modified Pfirrmann Scale) did not predict symptom persistence or radiographic fusion failure. Patients with high-grade disc disease experienced symptom relief. The authors found no predictors of treatment failure. Conclusions The number of patients undergoing motion segment–sparing fusions of symptomatic chronic SP can be safely increased to include patients with Grade I spondylolisthesis as well as high-grade disc disease. Female patients with bilateral L-5 SP and low lordotic angles may be better served by a posterior spinal fusion from L-5 to S-1.