Periodontitis is a series of inflammatory processes caused by bacterial infection. Parathyroid hormone (PTH) plays a critical role in bone remodeling. The present study aimed to investigate the influences of PTH on human bone marrow mesenchymal stem cells (HBMSCs) pretreated with lipopolysaccharide (LPS). The proliferative ability was measured using cell counting kit-8 (CCK-8) and flow cytometry. The optimal concentrations of PTH and LPS were determined using alkaline phosphatase (ALP) activity assay, ALP staining, and Alizarin Red staining. Osteogenic differentiation was further assessed by quantitative reverse-transcription polymerase chain reaction (RT-qPCR), Western blot analysis, and immunofluorescence staining. PTH had no effects on the proliferation of HBMSCs. Also, 100 ng/ml LPS significantly inhibited HBMSC osteogenesis, while 10 −9 mol/l PTH was considered as the optimal concentration to reverse the adverse effects. Mechanistically, c-Jun N-terminal kinase (JNK) phosphorylation was activated by PTH in LPS-induced HBMSCs. SP600125, a selective inhibitor targeting JNK mitogen-activated protein kinase (MAPK) signaling, weakened the effects of PTH. Taken together, the findings revealed the role and mechanism of PTH and JNK pathway in promoting the osteogenic differentiation of LPS-induced HBMSCs, which offered an alternative for treating periodontal diseases.

Calcium disturbances in the critically ill coincide with elevations of proinflammatory cytokines. The effects of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) on parathyroid hormone (PTH) secretion were investigated. IL-6 and TNF-α had no acute effect on PTH secretion in extracellular Ca 2+ concentrations of 0.5, 1.25 and 3.0 mM. In contrast to TNF-α, cultures for 24 h in the presence of 10 ng/mL of IL-6 showed decreased PTH secretion by 51% and 29% in 0.5 mM and 1.25 mMCa 2+ respectively. Neither IL-6 nor TNF-α, affected cytoplasmic Ca 2+ of the cells. We conclude that PTH secretion in vitro can be suppressed by IL-6 at clinically relevant concentrations. This suppression may aggravate hypocalcemia of the critically ill and attenuate the conventionally strong stimulation of the PTH release by reduction in serum calcium.

Female rats were given 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), 0.25 μg per 100 g body weight (bw), 25-hydroxyvitamin D 3 (25(OH)D 3 ), 1.7 μg/100 g bw or 24,25-dihydroxyvitamin D 3 (24,25(OH) 2 D 3 ) 1.7 μg/100 g bw, subcutaneously three times a week for 12 weeks. Traditional variables pertaining to calcium homeostasis and growth, i.e. blood and urine calcium (Ca) and phosphate (P), serum levels of vitamin D 3 metabolites parathyroid hormone, (PTH), calcitonin (CT), prolactin (PRL) and growth hormone (GH) were measured every four weeks. This data pool was correlated with bone matrix turnover parameters, i.e. serum levels of alkaline phosphatase (ALP) and urinary hydroxyproline (u-HYP) excretion. After 12 weeks of treatment, 1,25(OH) 2 D 3 significantly enhanced serum total and ionized Ca, urine Ca and urine P, and also diminished urine cAMP due to reduced renal function (creatinine clearance). However, 25(OH)D 3 administration had no such impact. 24,25(OH) 2 D 3 opposed the effect of 1,25(OH) 2 D 3 after 12 weeks by significantly augmenting serum P and diminishing serum levels of total Ca and ionized Ca. Cross sectional group analyses showed that criculating levels of ALP were directly related with serum 1,25(OH) 2 D 3 and inversely related to serum 24,25(OH) 2 D 3 and CT. Total u-HYP and per cent non-dialysable HYP (ndHYP) were reciprocally and positively correlated with serum PRL, respectively. However, no such relations were observed with serum GH. It appears that rats with elevated circulating levels of 1,25(OH) 2 D 3 exhibit increased bone resorption, while augmented 24,25(OH) 2 D 3 is associated with the opposite. Apparently, high bone turnover (i.e. reduced total urinary HYP and enhanced ndHYP) is associated with high serum PRL.

The effects of parathyroid hormone (PTH) on cytoplasmic free CA 2+ (Ca i 2+ ) and cAMP-formation were investigated in the rat osteosarcoma cell line UMR 106-01. In fura-2 loaded adherent single cells bPTH 1–34 (10 nM−1μM) induced a rapid transient increase in Ca i 2+ in 11% of the studied cells. In fura-2 tracings from UMR 106-01 cells in suspension, bPTH 1–34 (0.1 μM) induced a transient increase in Ca i 2+ in 20% of the experiments. The transient increase in Ca i 2+ seen in suspensions of cells was not abolished by addition of EGTA (2.5 mM) prior to challenge with PTH, suggesting that the increase in Ca i 2+ was derived from intracellular stores. A marked rapid increase in cAMP-formation was observed in all experiments with cells in suspension, also in the experiments where PTH did not affect Ca i 2+ . These data show that PTH causes a release of Ca 2+ from intracellular stores in a small percentage of osteosarcoma UMR 106-01 cells, and that PTH is capable of inducing an increase in cAMP-formation without affecting Ca i 2+ in osteoblasts.

We have used the chemically synthesized sequence of pre-pro-parathyroid hormone and several of its analogues to test the notion that the capacity of amphipathic peptides to aggregate in membranes and form ion-permeable channels correlates with their ability to function as signal sequences for secreted proteins. We found that pre-pro-parathyroid hormone (the signal sequence and pro-region of parathyroid hormone (M)), as well as some of its analogues, forms aggregates of monomers which are ion-permeable. The ion-permeable aggregates (2–3 monomers) formed by (M) are voltage-dependent and are more permeable for cations than for anions. The compounds which formed ion channels in bilayers also acted as potential signal sequences. We conclude that the ability of peptides to form ion-permeable pathways in bilayers may be correlated to their ability to function as signal peptides.

Native bovine parathyroid hormone (bPTH) was found to be readily cleaved with human leukocyte elastase to yield the fragments bPTH(1–41) and bPTH(42–84). These were then isolated by reverse-phase HPLC and characterised by gas-phase sequencing and amino acid analysis. The biological activities of these fragments were assessed in an adenylate cyclase bioassay using the rat osteosarcoma cell line UMR106. bPTH(1–41) was found to have approximately twice the molar potency of the native hormone from which it was derived, bPTH(42–84) had no biological activity and did not modulate the adenylate cyclase response to these cells to the native hormone. The possible physiological significance of these observations is discussed.

Monolayer culture of bovine parathyroid cells for 24 hours resulted in a right-shift of the dose-effect relationships for Ca 2+ -inhibition of parathyroid hormone (PTH) release and the dependence of the cytoplasmic Ca 2+ concentration (Ca 2+ ) on extracellular Ca 2+ as well as in a less suppressible hormone release. After 4 days of culture, hormone secretion was almost non-suppressible and Ca i 2+ increased poorly in response to a rise in extracelluiar Ca 2+ . Ionomycin, a Ca 2+ ionophore, raised Ca i 2+ , but there was only a small inhibition of PTH release and the correlation between Ca i 2+ and secretion was weak. A deteriorated Ca i 2+ regulation and a decreased inhibitory action of cytoplasmic Ca 2+ on PTH release were also found in ceils from human parathyroid adenomas. Functional dedifferentiation of the parathyroid cell thus results from both defective regulation and action of cytoplasmic Ca 2+ .