甲状旁腺激素和甲状旁腺激素相关蛋白在正常及骨性关节炎软骨中作用机制的研究进展

目的综述在正常和骨性关节炎(osteoarthritis,OA)的关节软骨及软骨下骨中,甲状旁腺激素(parathyroid hormone,PTH)和甲状旁腺激素相关蛋白(parathyroid hormone-related protein,PTHrP)的作用机制研究进展。方法广泛查阅近年来有关PTH和PTHrP对正常和OA关节软骨作用机制的文献,并进行总结与分析。结果 PTH和PTHrP可抑制OA软骨细胞的肥大分化及凋亡,促进其增殖,从而对OA软骨细胞起到保护作用;OA软骨下骨成骨细胞对PTH的反应下降。结论 PTH、PTHrP可能通过多种信号通路参与软骨降解和软骨下骨重塑,并对OA进展起到延缓和保护作用。     

甲状旁腺激素对髁突软骨细胞增殖、分化的影响

目的研究甲状旁腺激素(PTH)在持续性或间歇性作用下对大鼠髁突软骨细胞增殖、分化的影响。方法将分离后的雌性大鼠髁突软骨细胞根据PTH作用方式分为PTH持续应用组、PTH间歇应用组和空白对照组,MTT法检测不同PTH刺激方式对髁突软骨细胞增殖的影响,茜素红染色检测培养后第6、14天各组细胞矿化结节形成情况。提取各组成骨诱导培养第6、14天后细胞总RNA或总蛋白,碱性磷酸酶(ALP)检测试剂盒检测ALP活性,Western blot和Real-time PCR法检测软骨细胞增殖、分化及骨质形成相关蛋白(BSP、BMP2、OCN)和基因(COL2a1、COL10a1、RUNX2、OSX) mRNA的表达水平。结果第二代培养细胞爬片Ⅱ型胶原免疫组化染色结果均为阳性,表明培养细胞为髁突软骨细胞。髁突软骨细胞的增殖能力PTH持续应用组明显高于PTH间歇应用组和空白对照组(P 0. 05);PTH持续应用组形成矿化结节数量最少。结论持续性应用PTH能促进髁突软骨细胞增殖,抑制其成熟分化;间歇性应用PTH促进髁突软骨细胞分化及骨质形成,抑制其增殖。     

甲状腺机能亢进症患者骨密度及骨代谢改变

目的：探讨甲状腺机能亢进症（甲亢）患骨密度与骨代谢指标的改变。方法：本用二维骨密度仪测定65例甲亢患及38例健康对照骨密度,同时测定血清钙、碱性磷酸酶（AKP）、甲状旁腺激素（PTH）、降钙素（CT）、并计算PTH/CT比值及24小时尿钙值。分为3组：甲亢合并OP组;甲亢骨矿含量正常组及健康对照组。结果：甲亢合并OP组24小时尿钙、血AKP高于另两组（P＜0.05)甲亢组CT明显低于对照组,PTH/CT比值明显高于对照组,且甲亢合并OP组更明显（P＜0.05、P＜0.01)。结论：甲亢为高转换型OP,PTH、CT、PTH/CT比值对研究甲亢合并OP有重要参考价值。     

联合使用甲状旁腺激素和辛伐他汀对去卵巢大鼠骨质疏松症的治疗有叠加效应

目的探索联合使用甲状旁腺激素(PTH)和辛伐他汀(SIM)对去势大鼠骨质疏松的防治作用。方法 50只健康雌性SD大鼠随机行假手术(Sham,N=10)和切除双侧卵巢(OVX,N=40)手术后,OVX大鼠随机的分成4组:OVX组、SIM组、PTH组、PTH+SIM组。术后第1天开始给予药物治疗,SIM组:SIM灌胃(剂量5 mg/kg,每天1次),PTH组:PTH皮下注射(剂量60μg/kg,每周3次),PTH+SIM组:SIM灌胃和PTH皮下注射,剂量和用药频率和SIM组、PTH组相同,直至手术后12周为止,12时所有大鼠处死取胫骨行Micro-CT检测。结果结果表明SIM组、PTH组、PTH+SIM组和OVX组相比,胫骨近端都有较高的BMD、BV/TV、Tb.Th、Tb.N、Conn.D和较低的Tb.Sp,其中PTH+SIM组大鼠胫骨近端有最高的BMD、BV/TV、Tb.Th、Tb.N、Conn.D和最低Tb.Sp。SIM和PTH单独使用的效果明显低于他们联合使用对去卵巢大鼠骨质疏松的防治作用。结论联合使用甲状旁腺激素和辛伐他汀对去势大鼠骨质疏松的防治有叠加作用     

甲状旁腺激素防治骨质疏松的研究进展

甲状旁腺激素( parathyroid hormone,PTH)是一种肽类激素,调节钙磷代谢,是维持机体钙平衡的主要激素,其外周代谢在肾脏、骨及肝脏中进行,并直接作用于骨和肾,靶细胞为成骨细胞及肾小管细胞.PTH通过刺激成骨细胞增生分化、直接抑制成骨细胞凋亡,延长成骨作用时间,促进衬骨细胞向成骨细胞转化及刺激成骨细胞产...     

甲状旁腺素抑制人骨关节炎软骨细胞终末期分化的实验研究

目的:探讨甲状旁腺素(PTH)对人骨关节炎软骨细胞终末期分化的抑制作用。方法:分离和培养人骨关节炎软骨细胞,将其进行分组(PTH处理组和对照组),分别经PTH和盐水处理细胞,倒置显微镜观察细胞形态的变化,碱性磷酸酶(ALP)染色法检测ALP的分泌,RT-PCT法和WesternBlot法检测细胞内促终末期分化因子基因mR-NA和蛋白的表达。结果:人骨关节炎软骨细胞具有终末期成熟分化的特征,与对照组相比,PTH明显降低ALP染色的强度,显著降低细胞内促终末期分化基因mRNA和蛋白的表达。结论:PTH具有抑制人骨关节炎软骨细胞终末期分化的作用。     

联合使用甲状旁腺激素和钙剂对骨质疏松的防治有叠加作用

目的探索联合使用甲状旁腺激素和钙剂对去势大鼠诱导骨质疏松的防治作用。方法 50只健康雌性SD大鼠随机行假手术(Sham,N=10)和切除双侧卵巢(OVX,N=40)手术后,OVX大鼠随机的分成4组:OVX组、CA组、PTH组、PTH+CA组。术后第一天PTH组及PTH+CA开始给予药物治疗:PTH皮下注射(剂量60μg/kg,每周3次)。术后CA组及PTH+CA组大鼠饮食中加入钙剂,其余组大鼠普通饮食,直至手术后12周为止,12时所有大鼠处死取胫骨行Micro-CT、硬组织切片检测。结果 CA组、PTH组、PTH+CA组和OVX组相比,胫骨近端都有较高的BMD、BV/TV、Tb.Th、Tb.N、Conn.D、骨矿化沉积率(MAR)和较低的Tb.Sp,其中PTH+CA组大鼠胫骨有最高的BMD、BV/TV、Tb.Th、Tb.N、Conn.D、MAR和最低Tb.Sp。钙剂和PTH单独使用的效果明显低于他们联合使用对去卵巢大鼠骨质疏松的防治作用。结论联合使用甲状旁腺激素和钙剂对去势大鼠骨质疏松的防治有叠加作用     

甲状旁腺激素相关蛋白的临床研究

目的：探讨慢性肾衰竭（CRF）患甲状旁腺激素（PTH）和甲状旁腺激素相关蛋白（PTHrP)与中医辨证分型的关系。方法：采用放免法测定92例CRF患和30例正常人血清PTH和血浆PTHrP含量,并按中医辨证分型,将CRF患分为5脾肾气虚,脾肾气阴两虚,肝肾阴虚,阴阳两虚四型,结果：四个不同证型中的血清PTH,血浆PTHrP含量较正常对照组明显升高,结论：（1）血清PTH可做为慢性肾衰竭中医辨证分型的参考指标;（2）血浆PTHrP不宜做为中医辨证的参考指标。     

甲状腺全切除术后测定甲状旁腺激素对预测低血钙发生的价值

目的 探讨甲状腺全切除术后甲状旁腺激素(PTH)测定在预测有症状低血钙方面的意义.方法 前瞻性地选择2010年6月至2011年12月期间在首都医科大学宣武医院普通外科甲状腺乳腺专业组同一个主诊医师小组接受甲状腺全切除术的连续45例患者,分别于术后1h测定PTH与血钙,并在住院期间每天监测PTH与血钙,记录出现低血钙的症状.利用受试者工作曲线分析预测低血钙的临界值.结果 共45例患者,有9例(20.0％)术后血钙正常;17例(37.8％)术后出现无症状低血钙;19例(42.2％)出现有症状低血钙,需要补充钙剂治疗.血钙正常者、无症状低血钙者及有症状低血钙者术后1 h PTH值分别为(40.5±23.7) ng/L、(18.3±9.1)ng/L及(7.6±4.2)ng/L,方差分析显示,P＜0.001.术后1 h PTH值≤13.4 ng/L可以预测患者将发生低血钙的相关症状,敏感性为94.7％,特异性为76.9％.结论 甲状腺术后1 h PTH值≤13.4 ng/L的患者发生低血钙相关症状的可能性较大,需要补充钙剂治疗以减少患者的不适症状.     

甲状旁腺激素与骨质疏松及其他疾病关系的临床研究

甲状旁腺激素(PTH)是由甲状旁腺主细胞合成、分泌的由84个氨基酸组成的单链多肽。PTH为生命所必需，是调节钙、磷代谢、维持机体钙平衡的主要激素，靶细胞为成骨细胞及。肾小管细胞。有研究表明，中枢神经系统可能是PTH的另一靶器官，此外，PTH对心脏及调节平滑肌的作用也有研     

Present and future scope of recombinant parathyroid hormone therapy in orthopaedics

Parathyroid Hormone (PTH) has a significant role in calcium metabolism. Its intermittent administration has an anabolic effect on bone mineralization. Teriparatide (PTH 1-34), a recombinant form of parathyroid hormone, is useful in the treatment of osteoporosis, fracture healing, non-union, stress fracture, augmentation of implant fixation with bone, and chondroprotection in osteoarthritis. The present review article will elaborate on the potential approved uses of recombinant PTH in orthopedics and its evolving role in the management of fracture osteosynthesis and other common challenging bone pathologies.     

Differential effects of parathyroid hormone on chick growth plate and articular chondrocytes

Summary Parathyroid hormone (PTH) binds specifically to the hypertrophic region of growth plate cartilage [16]. This specific binding suggests a role for this hormone in chondrocyte maturation. Enzymatically isolated chick articular and growth plate chondrocytes grown in monolayer culture were used to assay the direct effects of PTH on chondrocytes. The articular chondrocytes were unresponsive to PTH. The growth plate chondrocytes, however, demonstrated a marked mitogenic response to PTH, with a 39-fold increase of [³H]-thymidine incorporation into DNA. PTH also affected matrix production by the growth plate chondrocytes causing a twofold stimulation of proteoglycan synthesis as determined by the rate of ³⁵SO₄ incorporated into matrix macromolecules. Furthermore, PTH depressed collagen synthesis as measured by [³H]-proline incorporation. PTH caused a 12-fold increase in intracellular cAMP in growth plate chondrocytes but no increase in the articular cells. This specificity of PTH for growth plate chondrocytes suggests a possible regulatory role in enchondral ossification.     

Osteoporotic fracture and parathyroid hormone

Osteoporosis and age-related bone loss is associated with changes in bone remodeling characterized by decreased bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Stimulating the function of bone-forming osteoblasts, is the preferred pharmacological intervention for osteoporosis. Recombinant parathyroid hormone (PTH), PTH(1-34), is an anabolic agent with proven benefits to bone strength and has been characterized as a potential therapy for skeletal repair. In spite of PTH's clinical use, safety is a major consideration for long-term treatment. Studies have demonstrated that intermittent PTH treatment enhances and accelerates the skeletal repair process via a number of mechanisms. Recent research into the molecular mechanism of PTH action on bone tissue has led to the development of PTH analogs to control osteoporotic fractures. This review summarizes a number of advances made in the field of PTH and bone fracture to combat these injuries in humans and in animal models. The ultimate goal of providing an alternative to PTH, currently the sole anabolic therapy in clinical use, to promote bone formation and improve bone strength in the aging population is yet to be achieved.     

Subchondral bone fragility with meniscal tear accelerates and parathyroid hormone decelerates articular cartilage degeneration in rat osteoarthritis model

The aims of this study were to investigate the influence of subchondral bone fragility (SBF) on the progression of the knee osteoarthritis by using a novel rat model, and to examine the preventive effect of parathyroid hormone (PTH) on cartilage degeneration. First, 40 rats were assigned to the following four groups: Sham, SBF, Medial meniscal tear (MMT), and MMT + SBF groups. In SBF and MMT + SBF groups, we induced SBF by microdrilling the subchondral bone. Second, 10 additional rats were randomly assigned to the following two groups: MMT + SBF + saline and MMT + SBF + PTH groups. Osteoarthritic changes in the articular cartilage and subchondral bone were evaluated using safranin‐O/fast green staining, matrix metalloproteinase‐13 (MMP‐13), and type X collagen immunohistochemistry, toluidine blue staining, and micro‐CT scanning. The combination of SBF and meniscal tear increased the number of mast cells in the subchondral bone, and led to the abnormal subchondral bone microarchitecture, such as abnormally decreased trabecular number and increased trabecular thickness, compared with meniscal tear alone. Moreover, SBF with meniscal tear enhanced articular cartilage degeneration and increased the expression of MMP‐13 and type X collagen, compared with meniscal tear alone. The administration of PTH decreased the number of mast cells in the subchondral bone and improved the microstructural parameters of the subchondral bone, and delayed the progression of articular cartilage degeneration. These results suggest that SBF is one of the factors underlying the osteoarthritis development, especially in knees with traumatic osteoarthritis, and that the administration of PTH is a potential therapeutic treatment for preventing OA progression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1959–1968, 2018.

     

Use of osmotic minipumps for delivery of parathyroid hormone

Summary To determine if osmotic minipumps can be used for the local delivery of parathyroid hormone (PTH), we examined the bone resorbing activity of PTH in minipumps, either removed and assayed in bone organ cultures or released over rat calvaria. Biological activity of PTH was maintained for up to 6 days when the hormone solution contained serum and the minipumps and tubing were siliconized and flushed with diluent prior to use. Addition of cysteine did not enhance activity.     

Thyroidectomy and parathyroid hormone: tracing hypocalcemia-prone patients

BACKGROUND: The aim of this prospective study was to identify patients at high risk of developing hypocalcemia after thyroidectomy on the basis of the parathyroid hormone (PTH) level on the first postoperative day. METHODS: We included 160 patients undergoing total thyroidectomy in a period of 6 months by the same surgical team in this study. In all patients the PTH level was measured before surgery on the day of surgery (PTH1), and on the first postoperative day (PTH2), whereas serum calcium level was measured daily until discharge. Patients were classified as hypocalcemic if they had a serum calcium level less than the normal range on the first postoperative day, independently of symptoms of hypocalcemia. RESULTS: At an average follow-up period of 5.9 months (range, 4-9 mo), 66 patients were considered hypocalcemic, 57 patients (35.6%) had a transient hypocalcemia, and 9 patients (5.6%) required calcium-vitamin D supplementation for persistent hypocalcemia. The mean PTH1 value was 54.4 +/- 17.2 pg/mL (median, 53.85 pg/mL), the mean PTH2 value was 22.8 +/- 13.3 pg/mL (median, 21 pg/mL). The mean PTH decrease in value was 51.54% +/- 27.4% (median, 51.83%; range, 4%-94%) and 43.7% of patients presented a PTH decrease of more than 50%. The presence of a postoperative hypocalcemia was statistical correlated both with the PTH2 level and with the PTH drop percent value (P < .001 and P = .002, respectively). With the use of the receiver operating characteristic curve, the maximum sum of the sensitivity and specificity for the correlation of PTH2 levels and hypocalcemia occurred at a PTH2 level of 9.6 pg/mL. CONCLUSIONS: The PTH measurement on the first postoperative day may be considered a useful method to predict postthyroidectomy hypocalcemia, thus avoiding prolonged hospitalization. Moreover, PTH dosage at first postoperative day is more reliable and less expensive than intraoperative quick PTH assay.     

甲状腺围术期甲状旁腺素与术后低钙血症的关系

目的探讨甲状腺围术期血清甲状旁腺素(PTH)的变化规律及其与甲状腺术后低钙血症(PHC)的相关关系。方法 2007年1月至2008年6月甲状腺手术患者322例,分别于术前1d、术中切除腺体后15min、术后第1天、术后第4天测定血清PTH及血清钙。结果甲状腺术后PTH比术前明显下降;PHC组的术中PTH明显低于正常血钙组的术中PTH;术中PTH低于正常值下限的患者PHC的发生率高于术中PTH正常的患者,差异均有统计学意义。结论甲状腺手术会影响甲状旁腺分泌PTH水平,术中PTH低于正常值下限可作为早期预测PHC的重要指标。     

Development of a parathyroid hormone-controlled release system as a potential surgical treatment for hypoparathyroidism

Background/Purpose

The aim of this study was to develop a surgically implantable controlled release delivery system for parathyroid hormone (PTH) that will maintain calcium homeostasis without the adverse side effects of long-term calcium and vitamin D replacement and can be used for the treatment of hypoparathyroidism.

Methods

Biodegradable poly(lactide-co-glycolide) (PLGA) microspheres loaded with PTH were made using a modification of the double emulsion (water/oil/water) solvent evaporation technique. To simulate the release of PTH from microspheres after implantation in an animal, the in vitro release profile for the PTH microspheres was determined by incubating the PTH microspheres in phosphate-buffered saline, serially sampling the effluent, and determining the concentration of PTH in the effluent over time using an enzyme-linked immunosorbent assay.

Results

(1) PTH was successfully incorporated into PLGA microspheres. (2) Controlled release of PTH was demonstrated in vitro over a 3-week period. (3) Release of physiological significant concentrations of PTH was achieved using this methodology.

Conclusions

Controlled release of physiological concentrations of PTH can be achieved using PLGA microsphere encapsulation.