Regulatory function and mechanism of autophagy on osteoclast / 中国骨伤

Osteoclast (OC) is multinucleated, bone-resorbing cells originated from monocyte/macrophage lineage of cells, excessive production and abnormal activation of which could lead to many bone metabolic diseases, such as osteoporosis, osteoarthritis, etc. Autophagy, as a highly conserved catabolic process in eukaryotic cells, which plays an important role in maintaining cell homeostasis, stress damage repair, proliferation and differentiation. Recent studies have found that autophagy was also involved in the regulation of osteoclast generation and bone resorption. On the one hand, autophagy could be induced and activated by various factors in osteocalsts, such as nutrient deficiency, hypoxia, receptor activator of nuclear factor(NF)-κB ligand(RANKL), inflammatory factors, wear particles, microgravity environment, etc, different inducible factors, such as RANKL, inflammatory factors, wear particles, could interact with each other and work together. On the other hand, activated autophagy is involved in regulating various stages of osteoclast differentiation and maturation, autophagy could promote proliferation of osteoclasts, inhibiting apoptosis, and promoting differentiation, migration and bone resorption of osteoclast. The classical autophagy signaling pathway mediated by mammalian target of rapamycin complex 1(mTORC1) is currently a focus of research, and it could be regulated by upstream signalings such as phosphatidylinositol 3 kinase(PI-3K)/protein kinase B (PKB), AMP-activated protein kinase(AMPK). However, the paper found that mTORC1-mediated autophagy may play a bidirectional role in regulating differentiation and function of osteoclasts, and its underlying mechanism needs to be further ciarified. Integrin αvβ3 and Rab protein families are important targets for autophagy to play a role in osteoclast migration and bone resorption, respectively. In view of important role of osteoclast in the occurrence of various bone diseases, it is of great significance to elucidate the role of autophagy on osteoclast and its mechanism for the treatment of various bone diseases. The autophagy pathway could be used as a new therapeutic target for the treatment of clinical bone diseases such as osteoporosis.

Minimum 2-Year Experience with Magnetically Controlled Growing Rods for the Treatment of Early-Onset Scoliosis: A Systematic Review

Magnetically controlled growing rods have been used to treat early-onset scoliosis for the last 9 years; however, few studies have been published, with only short-term follow-up. The aim of the present study is to systematically review the outcomes of magnetically controlled growing rods in the treatment of early-onset scoliosis with a minimum of 2-year follow-up. Studies were included if patients with early-onset scoliosis (scoliosis diagnosed before 10 years of age) underwent implantation of magnetically controlled growing rods with a minimum of 2-year follow-up. The literature review and data extraction followed the established preferred reporting items for systematic review and meta-analysis guidelines. Data of distraction frequency, number of distractions, distracted length, Cobb angle, kyphosis, T1–T12 length, and T1–S1 length preoperatively, postoperatively, and at final follow-up were collected. Data regarding complications and unplanned reoperations were also extracted. The mean values of these parameters were calculated, or pooled meta-analysis was performed if available. Ten articles were included in this systematic review, with a total of 116 patients and a follow-up period between 23 and 61 months. The mean preoperative Cobb angle and kyphosis angle were 60.1° and 38.0°, respectively, and improved to 35.4° and 26.1° postoperatively. At final follow-up, the Cobb and kyphosis angles were maintained at 36.9° and 36.0°, respectively. The average preoperative T1–T12 and T1–S1 lengths were 180.6 mm and 293.6 mm, respectively, and increased to 198.3 mm and 320.3 mm postoperatively. T1–T12 and T1–S1 lengths were 212.3 mm and 339.3 mm at final follow-up, respectively. The overall rate of patients with complications was 48% (95% confidence interval [CI], 0.38–0.58) and unplanned reoperation 44% (95% CI, 0.33–0.55) after sensitivity analysis. The current evidence from different countries with a minimum of a 2-year follow-up suggests that magnetically controlled growing rods are an effective technique to treat pediatric scoliosis and promote spine growth. However, nearly half of patients still developed complications or required unplanned reoperations.