NELL-1促成骨和成软骨的作用机制及应用前景

NELL-1（neural epidermal growth factor-like 1）是一种对骨软骨细胞系具有高度特异性的生长因子,因其局部诱导骨形成的效应而受到密切关注;另外,它还具有作为全身治疗药物的成骨潜能以及促软骨形成的功能。促成骨方面,NELL-1主要通过Runx、MAPK信号通路、经典Wnt信号通路起作用,和经典的成骨因子BMPs存在协同作用。最近几年,由于生物信息学和高通量RNA测序的不断进步,研究者也发现了NELL-1促成骨分化时RNA网络的潜在调控作用。而NELL-1的促软骨形成活性主要依赖于Runx3介导的Ihh信号转导。本文主要就NELL-1促进成骨和成软骨的相关机制,以及其在骨组织再生、软骨组织再生领域的应用作一综述。     

牙囊在牙萌出的作用及其调控机制研究进展

牙齿的萌出是指牙齿从颌骨内向口腔移动,穿透颌骨与口腔黏膜,然后接触对颌牙达到功能位置的复杂过程,这一过程在时间和空间上均受到严格管控。牙囊是围绕在发育中牙胚周围的一层来源于外胚间充质的疏松结缔组织,它通过招募单核细胞以及调控骨吸收和骨形成在牙齿萌出过程中发挥关键作用。国内外学者对牙囊在牙齿萌出中的作用和机制研究甚多,现将研究进展作一综述。     

Expression of angiopoietin‐like protein 4 at the fracture site: Regulation by hypoxia and osteoblastic differentiation

Vascular disruption that occurs as a consequence of bone fracture, leads to hypoxia at the site of damage. Hypoxia regulates the expression of a number of genes that can modulate energy conservation, cell survival, tissue regeneration and angiogenesis. In this study we investigated the expression of Angiopoietin‐like 4, an adipocytokine that has additional roles in angiogenesis, at the fracture site. We demonstrate that Angptl4 mRNA expression increased early during fracture healing (day 3) returning close to baseline at day14. In the callus, Angptl4 mRNA was visualized in areas of condensing mesenchymal cells, callus cartilage and was especially high in mineralizing osteoblasts located in areas of new bone formation. In vitro, Angptl4 mRNA expression in osteoblasts increased under hypoxic conditions and in cells treated with the hypoxia mimetic desferrioxamine. Angptl4 levels were strongly induced at day 14 in differentiating MC3T3‐E1 osteoblastic cells. Exogenous ANGPTL4 increased expression of Runx2, Spp1, vegfa, and Alp mRNA in differentiating osteoblasts. We suggest that the distribution of Angptl4 in the callus may be driven by hypoxia and that Angptl4 may play a role in osteoblastic differentiation, and possibly angiogenesis via regulation of VEGF. Further studies could reveal a dual role for Angptl4 in angiogenesis and osteogenesis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1364–1373, 2015.     

Osteocytic Sclerostin Expression in Alveolar Bone in Rats With Diabetes Mellitus and Ligature‐Induced Periodontitis

Background: Osteocytic sclerostin inhibits bone formation, and its expression is stimulated by tumor necrosis factor (TNF)‐α. This study investigates sclerostin and TNF‐α expression in rats with diabetes mellitus (DM) and periodontitis. Methods: Rats were divided into control (C), periodontitis (P), and DM + periodontitis (DP) groups. After induction of DM by streptozotocin, periodontitis was induced by ligature. At day 0 (control) and at days 3 and 20 after induction of periodontitis, alveolar bone, osteoclasts, osteoid area, and TNF‐α and sclerostin expression were evaluated. Results: The distance between the cemento‐enamel junction and the alveolar bone crest of the DP group was longer than that of the P group at day 20 after induction of periodontitis, but the number of osteoclasts was not different. Osteoid area decreased in both the P and DP groups by day 3, but whereas sustained osteoid suppression was observed in the DP group at day 20, osteoid formation was increased in the P group. The number of sclerostin‐positive osteocytes increased in both groups at day 3, but the increased number of sclerostin‐positive osteocytes was maintained only in the DP group through day 20. The number of TNF‐α–positive cells increased more in the DP group than in the P group. Conclusions: Enhanced alveolar bone loss, suppressed bone formation, and prevalent TNF‐α expression were characteristic of the DP group compared with the P group. Suppressed bone formation in the DP group was observed simultaneously with increased sclerostin and TNF‐α expression. These results suggest that upregulated osteocytic sclerostin expression in periodontitis accompanied by DM may play a role in suppressed bone formation.     

Biofabrication of a PLGA–TCP‐based porous bioactive bone substitute with sustained release of icaritin

A phytomolecule, icaritin, has been identified and shown to be osteopromotive for the prevention of osteoporosis and osteonecrosis. This study aimed to produce a bioactive poly (l ‐lactide‐co‐glycolide)–tricalcium phosphate (PLGA–TCP)‐based porous scaffold incorporating the osteopromotive phytomolecule icaritin, using a fine spinning technology. Both the structure and the composition of icaritin‐releasing PLGA–TCP‐based scaffolds were evaluated by scanning electron microscopy (SEM). The porosity was quantified by both water absorption and micro‐computed tomography (micro‐CT). The mechanical properties were evaluated using a compression test. In vitro release of icaritin from the PLGA–TCP scaffold was quantified by high‐performance liquid chromatography (HPLC). The attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the composite scaffold were evaluated. Both an in vitro cytotoxicity test and an in vivo test via muscular implantation were conducted to confirm the scaffold's biocompatibility. The results showed that the PLGA–TCP–icaritin composite scaffold was porous, with interconnected macro‐ (about 480 µm) and micropores (2–15 µm). The mechanical properties of the PLGA–TCP–icaritin scaffold were comparable with those of the pure PLGA–TCP scaffold, yet was spinning direction‐dependent. Icaritin content was detected in the medium and increased with time. The PLGA–TCP–icaritin scaffold facilitated the attachment, proliferation and osteogenic differentiation of BMSCs. In vitro cytotoxicity test and in vivo intramuscular implantation showed that the composite scaffold had no toxicity with good biocompatibility. In conclusion, an osteopromotive phytomolecule, icaritin, was successfully incorporated into PLGA–TCP to form an innovative porous composite scaffold with sustained release of osteopromotive icaritin, and this scaffold had good biocompatibility and osteopromotion, suggesting its potential for orthopaedic applications. Copyright © 2012 John Wiley & Sons, Ltd.     

Rush钉矫治成骨不全儿童股骨畸形的疗效观察

目的探讨股骨多段截骨髓内钉固定矫治儿童成骨不全症所致股骨畸形的疗效,分析术后并发症的防治。方法 2007年1月至2013年12月,我院共收治成骨不全所致股骨畸形患儿28例,包括39根畸形股骨。年龄3岁7个月至14岁5个月,平均8岁4个月。术中将弯曲股骨行多段截骨矫形及髓内钉固定,平均截骨1.9(1~3)处,随机分为弹性针组与Rush钉组,其中20根股骨使用弹性髓内钉,19根股骨使用Rush钉。结果随访1年3个月至5年7个月,平均3年8个月。随访后期按Sanders评分标准评定髋关节功能:弹性针组优11例,良2例,中7例,差0例;Rush钉组优16例,良2例,中1例,差0例。结论多段截骨矫形后髓内钉内固定治疗儿童成骨不全所致股骨畸形,能有效矫正股骨弯曲畸形,改善下肢外观及力线关系,防止再骨折,提高患儿生活质量,效果明确。Rush髓内钉内固定效果满意,术后再骨折概率小,股骨不易再次弯曲变形,值得临床推广。