Application Of Parathyroid Hormone Research Articles

The progress in application of parathyroid hormone in craniomaxillofacial bone regeneration study

Parathyroid hormone(PTH)is synthesized and secreted by chief cell of Gley's glands which possesses dual functions of catabolism and anabolism. It regulates the proliferation and differentiation of multiple cell lines including osteoblast, osteoclast and skeletal lining cells. Furthermore, PTH activates various signaling pathways which control calcium, phosphorous' metabolism and bone conversion, accelerating the bone regeneration and reconstruction. However, the study of PTH in craniomaxillofacial bone regeneration is relatively less and whether the role of parathyroid glands and the mechanism of ossification are consistent with the long bone or not needs further investigation. This review focuses on the progress of PTH in craniomaxillofacial bone regeneration in recent years.

Efficiency of 48h vs. 24h Injection of Parathyroid Hormone for Amelioration of Osteopenic Spine Properties in Male Rats

Daily application of parathyroid hormone (PTH 1-34) is used for treatment of osteoporosis. It was investigated whether orchiectomy-induced osteoporotic changes in spine can be ameliorated by every 48h administration of PTH in aged male rats. Eight-month-old male Sprague-Dawley rats were sham operated (n=24) or orchiectomized (Orx, n=36) and maintained untreated over 12 weeks. Thereafter, both tibia underwent transverse metaphyseal osteotomy (Komrakova et al. 2011, J Endocrinol; 209:9-19) and rats were divided into 5 groups treated s.c. as follows: 1) sham vehicle; 2) sham PTH every 24h (PTH/24h); 3) Orx vehicle; 4) Orx PTH/24h; 5) Orx PTH every 48h (PTH/48h). PTH dosage was 40 �g/kg BW per injection. After 5 weeks, lumbar vertebral bodies were used in computed tomographical, biomechanical, histomorphological, ashing and gene expression analyses. Cortical and trabecular densities, biomechanical properties, serum osteocalcin level increased significantly after PTH treatments in all groups (yield load, sham: 232+17N, sham PTH/24h: 376+12N, Orx: 239+16N, Orx PTH/24h: 324+31N, Orx PTH/48h: 297+17N). Bone inorganic weight enhanced after daily PTH application in Orx rats. Bone gene expression did not differ (P>0.05) among the groups. Both PTH administration regimes (24h and 48h) improved impaired bone structure in osteopenic rats. Every 48h application was less effective, however, it improved bone properties to the level observed in healthy (sham) rats. Considering limitation of daily treatments known in humans, these results may be useful for further clinical studies.

Analysis of dynamics of degenerative and regenerative processes in the flexor and extensor collaterals of crushed sciatic nerve: Effects of parathyroid hormone

We performed morphological, histochemical, and electrophysiological analysis of changes in the state of the rat sciatic nerve after nerve crushing. The activity of Ca2+-dependent acidic phosphatase (AP) was measured in sections of the nerve fibers to trace the recovery of the nerve after its injury. The systemic application of parathyroid hormone (PTH) resulted in the acceleration of injured nerve recovery. Proliferation of both endoneurium and Schwann cells was observed on the 3rd day after the crushing of the ipsilateral extensor (N. peroneus communis) and flexor (N. gastrocnemius) nerve bundles. A complete recovery of the AP enzymatic activity was found on the 7–9th days after the crushing. From the 5th to 35th days after the crushing, we performed online registration and mathematical analysis of pulse activity. In the control experiments, from the 35th to 70th days, high-frequency stimulation of the nerves showed the regeneration of the extensor nerve only accompanied by alterations in fiber direction. In the presence of PTH, the regeneration was significantly accelerated and it was associated with early regeneration of the flexor nerve and more structured fiber morphology. We found a correlation between the electrophysiological and morphological data.

Stem cell mobilization versus stem cell homing: potential role for parathyroid hormone?

Stem cells are considered as potential candidates to regenerate the injured myocardium. It has been shown that stem cells are able to differentiate into cardiomyocytes, as recently reviewed.2 It is still an open question, however, whether such myocytes contribute to the functional recovery of the post-infarcted heart. This process is limited by the small number of cells that differentiate into cardiomyocytes, the limited coupling of pre-existing cardiomyocytes to these newly formed myocytes, and the question whether the overall increases in ejection fractions indeed depend on the amount of cardiomyocytes newly formed by stem cells. A specific pattern of matrix proteins may be expressed by these cells, they may mediate anti-apoptotic effects, or they may improve vascularization independent of a possible differentiation into cardiomyocytes. Such effects may be modified by stem cells acting in a paracrine manner. Irrespective of these open questions, research is ongoing to develop treatment protocols that increase the number of systemic stem cells that home to the injured myocardium.3,4 Zaruba et al. 1 used a novel and innovative approach to improve the homing of bone marrow-derived stem cells, as described in their article in the current issue of Cardiovascular Research . They tried to improve bone marrow-derived stem cell mobilization by application of parathyroid hormone (PTH), which affects … *Corresponding author. Tel. +49 641 99 47222; fax +49 641 99 47239. E-mail address : klaus-dieter.schlueter{at}physiologie.med.uni-giessen.de

Calcium-channel activation and matrix protein upregulation in bone cells in response to mechanical strain

Femur-derived osteoblasts cultured from rat femora were loaded with Fluo-3 using the AM ester. A quantifiable stretch was applied and [Ca(2+)]i levels monitored by analysis of fluorescent images obtained using an inverted microscope and laser scanning confocal imaging system. Application of a single pulse of tensile strain via an expandable membrane resulted in immediate increase in [Ca(2+)]i in a proportion of the cells, followed by a slow and steady decrease to prestimulation levels. Application of parathyroid hormone (10(-6) M) prior to mechanical stimulation potentiated the load-induced elevation of [Ca(2+)]i. Mechanically stimulating osteoblasts in Ca(2+)-free media or in the presence of either nifedipine (10 microM; L-type Ca(2+)-channel blocker) or thapsigargin (1 microM; depletes intracellular Ca(2+) stores) reduced strain-induced increases in [Ca(2+) ]i. Furthermore, strain-induced increases in [Ca(2+)]i were enhanced in the presence of Bayer K 8644 (500 nm), an agonist of L-type calcium channels. The effects of mechanical strain with and without inhibitors and agonists are described on the total cell population and on single cell responses. Application of strain and strain in the presence of the calcium-channel agonist Bay K 8644 to periosteal-derived osteoblasts increased levels of the extracellular matrix proteins osteopontin and osteocalcin within 24 h postload. This mechanically induced increase in osteopontin and osteocalcin was inhibited by the addition of the calcium-channel antagonist, nifedipine. Our results suggest an important role for L-type calcium channels and a thapsigargin-sensitive component in early mechanical strain transduction pathways in osteoblasts.

Voltage sensitivity of gap junction currents in rat osteoblast-like cells

The dependence of macroscopic gap junctional conductance ( g j) upon transjunctional voltage ( V j) was examined in 39 paired osteoblast-like (OB) cells from primary cultures using the double whole cell patch clamp technique. OB cells were derived from calvarial explants of new-born rats. Instantaneous current–voltage ( I j– V j) relationships of OB cell pairs ( n=6) were linear in the entire voltage range (−150≤ V j≤150 mV) examined. The steady-state I j– V j relationship was non-linear for V j≥±60 mV. The curve for the normalised steady-state junctional conductance–voltage relationship ( G ss/ G 0– V j) was bell-shaped, and was fitted with a two-state Boltzmann equation with a minimum conductance ( G min) of 0.2–0.3, and a half deactivation voltage ( V o) of ±83 mV. In two recordings unitary gap junction channel activity was observable. The linear I– V relationships revealed a single channel conductance of ∼100 pS. Application of parathyroid hormone (10 −8 M) had no effect on the voltage dependence nor the magnitude of macroscopic currents ( n=7).

Electrophysiological responses of osteoclasts to hormones.

Electrophysiological measurements were carried out on osteoclasts in vitro. Such isolated osteoclasts are able to resorb bone in vitro and contract in response to calcitonin (CT). Our measurements show that individual osteoclasts respond to CT with a significant transient hyperpolarization of membrane potential. Application of parathyroid hormone (PTH) and dibutyryl cAMP produced a transient hyperpolarization in some osteoclasts. Measurements on an osteoblastlike line (ROS 17/2.8) showed a sustained hyperpolarizing response to CT, which is similar to but smaller than the hyperpolarizing response to PTH and dibutyryl cAMP in this and some other osteoblastlike lines. In contrast to osteoblastlike cells, the osteoclasts have no long term membrane potential response to CT, to PTH, or to dibutyryl cAMP. These results show that there are distinct differences between osteoclasts and osteoblasts in their ion transport responses to hormones.