甲状旁腺激素对种植体骨结合影响的研究现状

甲状旁腺激素(parathyroid hormone,PTH)因具有调节机体钙、磷代谢的重要作用,而被广泛应用于骨质疏松症的临床治疗。研究发现PTH在骨组织代谢过程中具有促进骨形成和骨吸收的双重效应,其最终的作用效果与给药方式和剂量等因素有密切的关系。另外,PTH被证明对促进种植体骨结合具有积极作用。但是其具体作用机制、使用方法和剂量等问题仍待进一步研究。本文就目前关于甲状旁腺激素对种植体骨结合影响的研究作一综述。     

间断使用甲状旁腺激素对卵巢切除小鼠胫骨钛种植体植入后的骨吸收的影响

连续性使用甲状旁腺激素(PTH)将促进骨吸收，而间断性使用PTH据报道可加速骨形成。本研究将螺纹状钛种植体植入卵巢切除鼠的胫骨，观察甲状旁腺激素(1～34)对骨吸收的效应。     

局部应用甲状旁腺激素调控颌骨再生的研究进展

甲状旁腺激素(parathyroid hormone, PTH)是由甲状旁腺主细胞合成和分泌的多肽分子, 是维持体内钙磷代谢平衡的重要激素, 具有促进骨形成和骨吸收的双重作用, 在临床上通过间歇性小剂量皮下注射促进成骨。为避免皮下注射存在的患者依从性差、靶器官利用度低、注射部位疼痛等问题, 近年来PTH的局部应用受到关注。本文就PTH局部应用的方式以及局部应用时促进颌骨再生研究作一综述, 旨在为PTH局部应用和研究提供参考。     

骨保护因子及其配体调控骨吸收的研究进展

成骨细胞或骨髓基质细胞在破骨细胞分化、激活过程中起重要作用。骨保护因子及其配体是各种亲骨性因子、骨代谢激素、药物调节骨代谢的核心因子。其中,骨保护因子是抑制破骨细胞骨吸收功能的核心因子,通过阻断其配体——破骨细胞分化因子对骨吸收的激活作用来调控骨代谢的平衡。因此,骨保护因子在治疗多种骨病中具有巨大潜力,有望成为治疗骨质疏松症的理想药剂。     

骨保护因子及其配体调控骨吸收的研究进展

成骨细胞或骨髓基质细胞在破骨细胞分化、激活过程中起重要作用。骨保护因子及其配体是各种亲骨性因子、骨代谢激素、药物调节骨代谢的核心因子。其中，骨保护因子是抑制破骨细胞骨吸收功能的核心因子，通过阻断其配体——破骨细胞分化因子对骨吸收的激活作用来调控骨代谢的平衡。因此，骨保护因子在治疗多种骨病中具有巨大潜力，有望成为治疗骨质疏松症的理想药剂。     

神经系统对骨代谢的影响

骨代谢和骨的内稳态是由骨吸收和骨形成两个过程共同维持的。近年来,越来越多的研究发现,神经系统参与骨发育、骨代谢的调节,以及骨的修复与再生。神经系统对骨代谢的调控主要是通过其分泌的神经递质及其广泛的外周神经突触实现的。在此,我们针对神经系统如何调节骨发育和骨代谢这一问题加以综述。主要内容包括交感神经、感觉神经和中枢神经系统的作用;血清素、瘦素、P物质、降钙素基因相关肽、SEMA等神经递质的作用机制。     

双磷酸盐类药物用于牙周炎治疗的研究进展

牙周炎是一种由致病菌引起的炎症破坏性疾病，可造成包括牙槽骨吸收在内的一系列牙周组织破坏。双磷酸盐类（BPs）药物具有调节骨吸收、潜在性促进骨形成的作用；在对动物实验性牙周炎的治疗中表现出抗炎和阻断骨吸收的作用；并已逐渐应用于人牙周炎的辅助性治疗。本文就BPs对牙槽骨代谢调节的机制和牙周炎治疗应用方面的新进展作一综述。     

微小RNA对成骨调控作用的研究进展

] 成骨细胞的分化和功能调控需由体内多种激素和局部产生的细胞因子协同完成。miRNAs (microRNAs) 是单股非编码的 RNAs 小分子,长度在 20~24个核苷酸大小。它通过与目标 RNA 基因的特定序列结合,参与基因转录后水平的调控。研究表明,miRNA 能够调控成骨细胞、破骨细胞和软骨细胞的增殖和分化,维持骨形成和骨吸收的平衡,调控软骨的骨化,是生物器官发育和某些骨代谢疾病的重要调控因子。miRNA 的发现, 揭示了基因组非编码区域蕴涵着重要的功能。因此,利用 miRNA治疗临床骨代谢疾病和修复骨缺损具有潜在的临床应用前景。本文对 miRNA 在骨形成过程中的调控作用及其研究进展作一综述。     

糖酵解与骨代谢关系的研究进展

骨骼是一个动态器官，其不断通过成骨细胞介导的骨形成与破骨细胞介导的骨吸收进行骨重建，维持自身骨代谢动态平衡，保持其结构稳定。在成骨细胞与破骨细胞的生理活动中，葡萄糖源源不断地为其提供能量，保证骨代谢平衡稳定。近年来，葡萄糖代谢方式之一糖酵解被认为与骨代谢过程密切相关。糖酵解途径本身、相关酶与代谢产物均被证明参与成骨细胞与破骨细胞的分化与功能调节，影响骨代谢平衡。本文就糖酵解途径与骨代谢的关系进行综述，并期望对寻找骨代谢相关疾病潜在治疗靶点提供新的思路。     

P物质与骨代谢关系的研究进展

P物质在骨代谢过程中起着重要作用，它在骨修复与重建过程中的作用逐渐成为人们研究的热点。作者重点就P物质在骨形成和骨吸收中作用的研究进展，尤其是在正畸过程中牙周组织的改建方面加以阐述，为进一步明确P物质在骨代谢过程中的作用机制提供理论依据     

Parathyroid hormone protects against periodontitis-associated bone loss

Parathyroid hormone (PTH) functions as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. In addition to the well-established catabolic effects (activation of bone resorption) of PTH, it is now recognized that intermittent PTH administration has anabolic effects (promotion of bone formation). The aim of this study was to investigate whether intermittent administration of PTH in rodents would block the alveolar bone loss observed in rats when a ligature model of periodontitis is used. Morphometric analysis showed that intermittent PTH administration (40 microg/kg) was able to protect the tooth site from periodontitis-induced bone resorption. In addition, there was a significant reduction in the number of inflammatory cells at the marginal gingival area in sections obtained from animals receiving PTH compared with control animals. These findings demonstrated that intermittent PTH administration was able to protect against periodontitis-associated bone loss in a rodent model.     

Parathyroid hormone and its effects on dental tissues

In the current era, various pharmacological agents exist for osteoporosis management, and synthetic parathyroid hormone (PTH) (Teriparatide, Forteo) is one of the treatment options. Depending on the timing of administration, PTH has a unique ability to cause both bone apposition and bone resorption. This review focuses on the effects of PTH on the bone, specifically the jaw bones mandible and maxilla. The article briefly describes the fundamental mechanism of PTH action at the molecular level, as well as in experimental animals and in humans. It differentiates intermittent administration of PTH, especially at doses tolerated by humans that increase bone strength and prevent bone fractures, from continuous use that may lead to bone loss. In particular, it shows how intermittent administration of PTH can play a significant role in periodontal repair and implant success via stimulation of bone mineral content especially in the pre-alveolar region.     

Diphenylhydantoin inhibits parathyroid hormone and prostaglandin E2-stimulated bone resorption in mouse calvaria without affecting cyclic AMP formation

The effect of diphenylhydantoin (DPH) on mouse calvarial bone metabolism was studied in vitro. DPH caused a dose-dependent, reversible inhibition of PTH and PGE2-stimulated bone resorption at concentrations above 20-30 micrograms/ml without affecting cyclic AMP formation. The inhibition was observed already after 60 min and was accompanied by a reduced release of the lysosomal enzymes beta-glucuronidase and beta-N-acetylglucosaminidase. The calcium antagonist Verapamil had similar effects on bone resorption and lysosomal enzyme release and it is suggested that DPH influences bone resorption by interfering with calcium fluxes across osteoclastic cell membranes resulting in low intracellular calcium levels and reduced exocytotic processes.     

Diphenylhydantoin inhibits parathyroid hormone and prostaglandin E2-stimulated bone resorption in mouse calvaria without affecting cyclic AMP formation

The effect of diphenylhydantoin (DPH) on mouse calvarial bone metabolism was studied in vitro. DPH caused a dose-dependent, reversible inhibition of PTH and PGE₂-stimulated bone resorption at concentrations above 20–30 μg/ml without affecting cyclic AMP formation The inhibition was observed already after 60 min and was accompanied by a reduced release of the lysosomal enzymes β-glucuronidase and β-N-acetylglucosaminidase The calcium antagonist Verapamil® had similar effects on bone resorption and lysosomal enzyme release and it is suggested that DPH influences bone resorption by interfering with calcium fluxes across osteoclastic cell membranes resulting in low intracellular calcium levels and reduced exocytotic processes.     

Action of parathyroid hormone, with special reference to its anabolic effect on different kinds of tissues in rats (I).

The effect of parathyroid hormone (PTH) on the spongiosa of the proximal tibia and the alveolar bone in immature rats was studied using a time marker by the injection of lead acetate. 1) When intact rats were fed on a low calcium diet, the promotion of the apposition of the alveolar bone and the longitudinal formation as well as the resorption of the spongiosa were observed, but no change was detected in the serum calcium level. The resorption was more remarkable than the formation. 2) By parathyroidectomy (PTX) or thyroparathyroidectomy (TPTX) the effect described in 1) disappeared completely, but there subsequently occurred a fall of the serum calcium level and a marked inhibition of the formation and resorption. The decrease in the appositional formation was stronger than in the longitudinal formation. 3) When PTH was injected into the rats having undergone PTX or TPTX, all of the effects in 2) were reversed with the recovery of the apposition being at an extremely high rate. All the foregoing results indicate that PTH has an evident anabolic action in addition to the action of increasing the bone resorption and that the sensitivity to PTH is stronger in the periosteal bone than in the spongiosa.     

Histological functions of parathyroid hormone on bone formation and bone blood vessels

BackgroundThe intermittent administration of parathyroid hormone (PTH) has been prescribed to osteoporotic patients due to its bone anabolic effects. In addition to its actions on bone cells, PTH appears to affect bone-specific blood vessels. These blood vessels are derived from bone marrow sinusoids, which express EphB4, a hallmark of veinous vascular endothelial cells. Given the presence of osteo–vascular interactions, it is important to elucidate the effects of PTH on bone cells and blood vessels in murine models.HighlightsPTH stimulates preosteoblastic proliferation and osteoblastic bone formation. The former appears to be directly affected by PTH, whereas the latter requires osteoclast-mediated coupling. The administration of PTH through high-frequency dosage schemes accelerates bone turnover featuring remodeling-based bone formation, whereas low-frequency schemes cause mainly remodeling-based and partly modeling-based bone formation. Normally, many blood vessels lack alpha smooth muscle actin (αSMA)-immunoreactive vascular muscle cells surrounding basement membranes, indicating them being capillaries. However, PTH administration increases the number of blood vessels surrounded by αSMA-positive cells. These αSMA-positive cells spread out of blood vessels and express alkaline phosphatase and c-kit, suggesting their potential to differentiate into osteogenic and vascular endothelial/perivascular cells. Unlike bone cells, αSMA-positive cells did not appear in the periphery of blood vessels in the kidney and liver, and the thickness of the tunica media did not change regardless of PTH administration.ConclusionBased on the results of the study and presence of osseous–vascular interactions, PTH appears to influence not only osteoblastic cells, but also blood vessels in bone.     

Intermittent administration of parathyroid hormone improves bone quality and quantity around implants in rat tibiae

ObjectivesIntermittent injection of parathyroid hormone (PTH) is used to treat osteoporosis. The concept of bone quality was updated 20 years ago; however, these updates have not been adopted in implant dentistry. This study aimed to investigate the effects of intermittent administration of PTH on bone quality around implants in rat tibiae.MethodsGrade IV-titanium-threaded implants that were 3.5 mm long and 2.0 mm wide were placed in a randomly selected side of the proximal tibiae of 12-week-old female Wistar rats. Three weeks after implant placement, the rats were randomly divided into PTH-administration and saline-injection groups (PTH and VC, respectively; n = 7 per group). Micro-computed tomographical, histomorphometric, and immunohistochemical analyses were performed to evaluate bone quality and quantity surrounding the implants.ResultsPTH significantly increased bone volume and bone mineral density in bones not associated with the implants as compared to these values in the VC group. PTH significantly increased bone area and the amount of collagen within the total inside areas of all implant threads compared to that observed in VC. Moreover, PTH significantly increased the number of osteoblasts, osteocytes, and osteoclasts in the total inside and/or outside areas of all implant threads and altered the ratio of type I and III collagen to total collagen fibers.ConclusionsWithin the limitations of this study, intermittent administration of PTH improved both bone quantity and bone quality based on the types and numbers of bone cells and the types of collagen fibers surrounding implants placed into rat tibiae.     

Effect of phenytoin on rat bone resorption in vitro

Effects of phenytoin (DPH) on parathyroid hormone (PTH)- and 1,25-dihydroxyvitamin D3(1,25DHCC)-mediated bone resorption in bone organ culture were evaluated: it markedly inhibited the actions of both. However, PTH tended to overcome the initial effects of DPH, whereas bone resorption due to 1,25DHCC remained depressed as if DPH treatment had continued. Thus DPH-induced bone abnormalities may involve a greater direct effect on 1,25DHCC regulation of bone homeostasis than on PTH.     

Topical and intermittent application of parathyroid hormone recovers alveolar bone loss in rat experimental periodontitis

Tokunaga K, Seto H, Ohba H, Mihara C, Hama H, Horibe M, Yoneda S, Nagata T. Topical and intermittent application of parathyroid hormone recovers alveolar bone loss in rat experimental periodontitis. J Periodont Res 2011; 46: 655–662. © 2011 John Wiley & Sons A/S Background and Objective: Periodontitis is characterized by periodontal tissue inflammation and alveolar bone loss. The intermittent administration of parathyroid hormone (PTH), a major regulator of bone remodeling, has been demonstrated to stimulate osteoblastic activity. Although the systemic administration of PTH has been reported to protect against periodontitis‐associated bone loss, the effect of the topical administration of PTH is unclear. In this study, the effect of intermittent administration of PTH on osteoblastic differentiation was examined in cultured calvaria cells and then the effect of topical and intermittent administration of PTH was determined by measuring the recovery of alveolar bone loss after inducing experimental periodontitis in rats. Material and Methods: Alkaline phosphatase activity and bone nodule formation were measured in fetal rat calvaria cells. Experimental periodontitis was induced by placing nylon ligature around rat maxillary molars for 20 d. After ligature removal (day 0), PTH was topically injected into buccal gingiva three times a week for 10 wk. Micro‐computed tomography analysis and histological examination were performed on days 35 and 70. Results: Intermittent exposure of PTH in calvaria cells increased alkaline phosphatase activity and bone nodule formation by 1.4‐ and 2.4‐fold, respectively. Ligature procedures induced marked alveolar bone loss around the molars on day 0 and greater bone recovery was observed in the PTH‐treated rats on day 70. An increase in osteoid formation on the surface of alveolar bone was detected in the PTH‐treated rats. Conclusion: Intermittent treatment with PTH stimulated osteoblastic differentiation in fetal rat calvaria cell cultures, and topical and intermittent administration of PTH recovered alveolar bone loss in rat experimental periodontitis.     

间充质干细胞调控破骨细胞分化及功能的研究进展

间充质干细胞(MSCs)对骨代谢的作用是多方面的。MSCs对破骨细胞和骨吸收的调控是其中一个很重要的方面。MSCs对破骨有双面的调节作用,可能促进或者抑制,取决于炎症环境的情况。在一些生理、病理环境下,MSCs通过分泌相关细胞因子对破骨细胞的形成及功能起正向调控作用。但在某些炎症状态下,MSCs可能也通过旁分泌作用实现对破骨细胞形成和分化的抑制作用,尤其是在体外共培养破骨细胞与MSCs,MSCs对破骨细胞的形成表现出抑制作用。了解MSCs对破骨细胞的调控作用,有助于了解炎症微环境下MSCs对骨丢失的治疗潜能。