Pulsed electromagnetic fields stimulate osteogenic differentiation and maturation of osteoblasts by upregulating the expression of BMPRII localized at the base of primary cilium

Pulsed electromagnetic fields (PEMFs) have been considered as a potential candidate for the prevention and treatment of osteoporosis, however, the mechanism of its action is still elusive. We have previously reported that 50 Hz 0.6 mT PEMFs stimulate osteoblastic differentiation and mineralization in a primary cilium- dependent manner, but did not know the reason. In the current study, we found that the PEMFs promoted osteogenic differentiation and maturation of rat calvarial osteoblasts (ROBs) by activating bone morphogenetic protein BMP-Smad1/5/8 signaling on the condition that primary cilia were normal. Further studies revealed that BMPRII, the primary binding receptor of BMP ligand, was readily and strongly upregulated by PEMF treatment and localized at the bases of primary cilia. Abrogation of primary cilia with small interfering RNA sequence targeting IFT88 abolished the PEMF-induced upregulation of BMPRII and its ciliary localization. Knockdown of BMPRII expression level with RNA interference had no effects on primary cilia but significantly decreased the promoting effect of PEMFs on osteoblastic differentiation and maturation. These results indicated that PEMFs stimulate osteogenic differentiation and maturation of osteoblast by primary cilium-mediated upregulation of BMPRII expression and subsequently activation of BMP-Smad1/5/8 signaling, and that BMPRII is the key component linking primary cilium and BMP-Smad1/5/8 pathway. This study has thus revealed the molecular mechanism for the osteogenic effect of PEMFs.     

Ⅰ期手术经后路病灶清除内固定治疗儿童胸椎结核

目的:探讨Ⅰ期手术经后路结核病灶清除植骨融合内固定治疗儿童胸椎结核的效果.方法:2005年6月至2010年12月采用病灶清除植骨融合内固定治疗儿童胸椎结核9例,其中男7例,女2例;年龄3～12岁,平均7岁;病史3个月～1年,平均6个月.患儿均有不同程度胸背痛、肋间神经痛以及脊柱后凸畸形,同时伴有低热、盗汗、消瘦等全身症状.术前X线片、CT、MRI检查提示病变部位多发生于T4-T9节段.胸段后凸角35°～72°,平均48.2°.术前脊髓功能ASIA分级:B级2例,C级5例,D级2例.术后定期复查X线片了解后凸角变化和椎间植骨融合情况,采用ASIA分级评定术后脊髓功能恢复情况.结果:术中无大血管或脊髓损伤,术后随访16～38个月,平均24个月.所有患儿结核症状消失,无结核复发、切口感染、窦道形成或内固定失败等并发症,复查血沉正常.术后4～8个月复查X线片提示椎间植骨均获骨性愈合,内固定位置正常.最后随访后凸角12°～30°,平均19.5°,脊髓功能ASIA分级:C级2例,D级2例,E级5例.脊髓功能均有不同程度改善.结论:Ⅰ期经后路清除胸椎结核病灶彻底,椎管减压可靠,矫形效果显著,行自体或同种异体骨植骨钉棒系统内固定可有效重建胸段脊柱的稳定性.     

Androgens have antiresorptive effects on trabecular disuse osteopenia independent from muscle atrophy

Aging hypogonadal men are at increased risk of osteoporosis and sarcopenia. Testosterone is a potentially appealing strategy to prevent simultaneous bone and muscle loss. The androgen receptor (AR) mediates antiresorptive effects on trabecular bone via osteoblast-lineage cells, as well as muscle-anabolic actions. Sex steroids also modify the skeletal response to mechanical loading. However, it is unclear whether the effects of androgens on bone remain effective independent of mechanical stimulation or rather require indirect androgen effects via muscle. This study aims to characterize the effects and underlying mechanisms of androgens on disuse osteosarcopenia. Adult male mice received a unilateral botulinum toxin (BTx) injection, and underwent sham surgery or orchidectomy (ORX) without or with testosterone (ORX + T) or dihydrotestosterone (ORX + DHT) replacement. Compared to the contralateral internal control hindlimb, acute trabecular number and bone volume loss was increased by ORX and partially prevented DHT. T was more efficient and increased BV/TV in both hindlimbs over sham values, although it did not reduce the detrimental effect of BTx. Both androgens and BTx regulated trabecular osteoclast surface as well as tartrate-resistant acid phosphatase expression. Androgens also prevented BTx-induced body weight loss but did not significantly influence paralysis or muscle atrophy. BTx and ORX both reduced cortical thickness via endosteal expansion, which was prevented by T but not DHT. In long-term follow-up, the residual trabecular bone volume deficit in sham-BTx hindlimbs was prevented by DHT but T restored it more efficiently to pre-treatment levels. Conditional AR deletion in late osteoblasts and osteocytes or in the satellite cell lineage increased age-related trabecular bone loss in both hindlimbs without influencing the effect of BTx on trabecular osteopenia. We conclude that androgens have antiresorptive effects on trabecular disuse osteopenia which do not require AR actions on bone via muscle or via osteocytes.     

Towards new material biomarkers for fracture risk

Osteoporosis is a prevalent bone condition, characterised by low bone mass and increased fracture risk. Currently, the gold standard for identifying osteoporosis and increased fracture risk is through quantification of bone mineral density (BMD) using dual energy X-ray absorption (DEXA). However, the risk of osteoporotic fracture is determined collectively by bone mass, architecture and physicochemistry of the mineral composite building blocks. Thus DEXA scans alone inevitably fail to fully discriminate individuals who will suffer a fragility fracture. This study examines trabecular bone at both ultrastructure and microarchitectural levels to provide a detailed material view of bone, and therefore provides a more comprehensive explanation of osteoporotic fracture risk. Physicochemical characterisation obtained through X-ray diffraction and infrared analysis indicated significant differences in apatite crystal chemistry and nanostructure between fracture and non-fracture groups. Further, this study, through considering the potential correlations between the chemical biomarkers and microarchitectural properties of trabecular bone, has investigated the relationship between bone mechanical properties (e.g. fragility) and physicochemical material features.