To improve the osteogenic property of bone repairing materials and to accelerate bone healing are major tasks in bone biomaterials research. The objective of this study was to investigate if the mechanical force could be used to accelerate bone formation in a bony defect in vivo. The calcium sulfate cement was implanted into the left distal femoral epiphyses surgically in 16 rats. The half of rats were subjected to external mechanical force via treadmill exercise, the exercise started at day 7 postoperatively for 30 consecutive days and at a constant speed 8 m?min21 for 45 min?day21, while the rest served as a control. The rats were scanned four times longitudinally after surgery using microcomputed tomography and newly formed bone was evaluated. After sacrificing, the femurs had biomechanical test of three-point bending and histological analysis. The results showed that bone healing under mechanical force were better than the control with residual defect areas of 0.6460.19 mm2 and 1.7860.39 mm2 (P,0.001), and the ultimate loads to failure under mechanical force were 69.5664.74 N, stronger than the control with ultimate loads to failure of 59.1767.48 N (P50.039). This suggests that the mechanical force might be used to improve new bone formation and potentially offer a clinical strategy to accelerate bone healing.
作者： 刊期： 2015年第01期
Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.
作者： 刊期： 2015年第01期
Age related defect of the osteogenic differentiation of mesenchymal stem cells (MSCs) plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation. Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5%elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats. Accordingly, there were much more reactive oxygen species (ROS) production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1 (SOD1) was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.
作者： 刊期： 2015年第01期
Modern warfare has caused a large number of severe extremity injuries, many of which become infected. In more recent conflicts, a pattern of co-infection with Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus has emerged. We attempted to recreate this pattern in an animal model to evaluate the role of vascularity in contaminated open fractures. Historically, it has been observed that infected bones frequently appear hypovascular, but vascularity in association with bone infection has not been examined in animal models. Adult rats underwent femur fracture and muscle crush injury followed by stabilization and bacterial contamination with A. baumannii complex and methicillin-resistant Staphylococcus aureus. Vascularity and perfusion were assessed by microCT angiography and SPECT scanning, respectively, at 1, 2 and 4 weeks after injury. Quantitative bacterial cultures were also obtained. Multi-bacterial infections were successfully created, with methicillin-resistant S. aureus predominating. There was overall increase in blood flow to injured limbs that was markedly greater in bacteria-inoculated limbs. Vessel volume was greater in the infected group. Quadriceps atrophy was seen in both groups, but was greater in the infected group. In this animal model, infected open fractures had greater perfusion and vascularity than non-infected limbs.
作者： 刊期： 2015年第01期
Transforming growth factor-beta (TGF-b)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-b/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-b (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-b/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-b/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and b-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-b/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics.
作者： 刊期： 2015年第01期
Severe burn injury triggers the body’s nonspecific adaptive responses to acute insult, including the systemic inflammatory and stress responses, as well as the sympathetic response to immobilization. These responses trigger inflammatory bone resorption followed by glucocorticoid-induced apoptosis of osteoblasts and probably osteocytes. Because these patients are catabolic, they suffer concomitant muscle wasting and negative nitrogen balance. The use of anabolic agents such as recombinant human growth hormone and oxandrolone results in improved bone mineral content and muscle strength after approximately 1 year. Use of bisphosphonates within the first 10 days of a severe burn completely blocks the resorptive bone loss and has the added advantage of appearing to preserve muscle protein from excessive breakdown. The mechanism for the protective effect on muscle is not currently known. However, if the effect of bisphosphonates on muscle can be confirmed, it raises the possibility that bone communicates with muscle.
作者： 刊期： 2015年第01期
Parathyroid hormone (PTH) secretion is characterized by an ultradian rhythm with tonic and pulsatile components. In healthy subjects, the majority of PTH is secreted in tonic fashion, whereas approximately 30%is secreted in low-amplitude and high-frequency bursts occurring every 10–20 min, superimposed on tonic secretion. Changes in the ultradian PTH secretion were shown to occur in patients with primary and secondary osteoporosis, with skeletal effects depending on the reciprocal modifications of pulsatile and tonic components. Indeed, pathophysiology of spontaneous PTH secretion remains an area potentially suitable to be explored, particularly in those conditions such as secondary forms of osteoporosis, in which conventional biochemical and densitometric parameters may not always give reliable diagnostic and therapeutic indications. This review will highlight the literature data supporting the hypothesis that changes of ultradian PTH secretion may be correlated with skeletal fragility in primary and secondary osteoporosis.
作者： 刊期： 2015年第01期
作者： 刊期： 2015年第01期
