No abstract

Recent experiments have explored the impact of Wnt/β-catenin signaling and Substance P (SP) on the regulation of osteogenesis. However, the molecular regulatory mechanisms of SP on the formation of osteoblasts is still unknown. In this study, we investigated the impact of SP on the differentiation of MC3T3-E1 cells. The osteogenic effect of SP was observed at different SP concentrations (ranging from 10−10 to 10−8 M). To unravel the underlying mechanism, the MC3T3-E1 cells were treated with SP after the pretreatment by neurokinin-1 (NK1) antagonists and Dickkopf-1 (DKK1) and gene expression levels of Wnt/β-catenin signaling pathway components, as well as osteoblast differentiation markers (collagen type I, alkaline phosphatase, osteocalcin, and Runx2), were measured using quantitative polymerase chain reaction (PCR). Furthermore, protein levels of Wnt/β-catenin signaling pathway were detected using Western blotting and the effects of SP, NK1 antagonist, and DKK1 on β-catenin activation were investigated by immunofluorescence staining. Our data indicated that SP (10−9 to 10−8 M) significantly up-regulated the expressions of osteoblastic genes. SP (10−8 M) also elevated the mRNA level of c-myc, cyclin D1, and lymphocyte enhancer factor-1 (Lef1), as well as c-myc and β-catenin protein levels, but decreased the expression of Tcf7 mRNA. Moreover, SP (10−8 M) promoted the transfer of β-catenin into nucleus. The effects of SP treatment were inhibited by the NK1 antagonist and DKK1. These findings suggest that SP may enhance differentiation of MC3T3-E1 cells via regulation of the Wnt/β-catenin signaling pathway.

Controversy exists regarding the clinical outcomes of reamed vs unreamed intramedullary nailing in the treatment of closed tibial fractures. This study assessed the effects of reamed vs unreamed intramedullary nailing for closed tibial fractures. The authors searched PubMed, EMBASE, BIOSIS, and the Cochrane Controlled Trials Register for randomized and quasi-randomized controlled clinical trials from January 1980 to June 2012 comparing reamed with unreamed intramedullary nailing for closed tibial fracture in adults. Primary outcomes were nonunion, delayed union, malunion, secondary procedure, failure of implants, compartment syndrome, infection, and knee pain. Eight randomized and 1 quasi-randomized clinical trials (1229 fractures) were included. No statistically significant differences were found between reamed and unreamed nailing groups in delayed union (P=.20), malunion (P=.28), infection (P=.36), compartment syndrome (P=.36), and knee pain (P=.93). The unreamed group had a higher rate of fracture nonunion than the reamed group (P=.02). The subgroup analysis of implant failures (broken screws vs broken nails) indicated that reamed nailing significantly reduced the risk of screw breakage (P<.001); however, there was no significant difference between reamed and unreamed intramedullary nailing in nail breakage (P=.94). The subgroup analysis of a secondary procedure showed that the reamed intramedullary nailing resulted in significantly lower risks of implant exchange (P=.01) and dynamization (P=.04); however, there was no significant difference in bone grafting rate (P=.73). Evidence comparing reamed with unreamed intramedullary nailing for closed tibial fractures indicates that reamed intramedullary nailing may lead to significantly lower risks of nonunion, screw failure, implant exchange, and dynamization without increasing operative complications.