Alpha-1 Antitrypsin Inhibits Cathepsin k and Osteoclastic Bone Mineral Resorption In Vitro

2016 ◽  
Author(s):  
Mohammad Akbar
Keyword(s):  
Bone Mineral ◽  
Cathepsin K ◽  
Alpha 1 Antitrypsin ◽  
Mineral Resorption

Characterization of the Serum a1-Antitripsine Level in Primary Spontaneous Pneumotorax Patients

2018 ◽  
Vol 69 (9) ◽  
pp. 2591-2593
Author(s):  
Cristina Grigorescu ◽  
Liviu Ciprian Gavril ◽  
Laura Gavril ◽  
Tiberiu Lunguleac ◽  
Bogdan Mihnea Ciuntu ◽  
...  
Keyword(s):  
Serum Level ◽  
Pulmonary Emphysema ◽  
Spontaneous Pneumothorax ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Determining Factor

Diagnosis of primary or idiopathic spontaneous pneumothorax is one of exclusion, and in fact defines an entity that may have a difficult or impossible cause to be highlighted by current means, we consider it appropriate to study these etiopathogenic aspects. There is a definite association between alpha-1 antitrypsin deficiency and pulmonary emphysema and indirect spontaneous pneumothorax secondary to an emphysematous pulmonary lesion. Dose of alpha-1 antitrypsin is an immunoturbinimetric method for in vitro determination of alpha-1 antitrypsin in human serum and plasma. This product is calibrated to be used for the Daytona RX analyzer. The serum level of alpha-1-antitrypsin is not a determining factor in the postoperative evolution characterized by the interval until air loss disappears, but certainly exerts some influence, the exact level of which remains to be determined.

scholarly journals Copper as Dietary Supplement for Bone Metabolism: A Review

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2246
Author(s):  
Mariangela Rondanelli ◽  
Milena Anna Faliva ◽  
Vittoria Infantino ◽  
Clara Gasparri ◽  
Giancarlo Iannello ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Bone Mineral ◽  
Animal Studies ◽  
Small Sample ◽  
Blood Levels ◽  
Mineral Density ◽  
Dietary Copper ◽  
Slowing Down ◽  
Copper Supplementation

While in vitro and animal studies of osteoblastic and osteoclastic activity as well as bone resistance for copper are numerous, and the results encouraging in terms of regulation, human studies are scarce. The aim of this narrative review was to investigate the correlation of blood copper, daily copper intake, and copper supplementation with bone mineral density. This review included 10 eligible studies: five studies concerned copper blood levels, one study concerned daily copper intake, and four studies concerned copper supplementation. Blood copper levels did not show statistically significant differences in four of the studies analyzed, while only one study showed differences between osteoporotic and healthy women, although only with women between 45 and 59 years of age and not between 60 and 80 years of age. The dietary copper intake among women with or without osteoporosis did not show any differences. Only one study with a small sample of subjects carried out these assessments; therefore, it is a topic that the literature must deepen with further studies. The two studies that analyzed the integration of copper (2.5–3 mg/day) only showed good results in terms of slowing down bone mineral loss and reducing resorption markers, confirming the effectiveness of copper supplementation on bone metabolism.

Cells in regenerating deer antler cartilage provide a microenvironment that supports osteoclast differentiation

2001 ◽  
Vol 204 (3) ◽  
pp. 443-455
Author(s):  
C. Faucheux ◽  
S. Nesbitt ◽  
M. Horton ◽  
J. Price
Keyword(s):  
Type I Collagen ◽  
Mononuclear Cells ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Collagen Matrix ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Deer Antler

Deer antlers are a rare example of mammalian epimorphic regeneration. Each year, the antlers re-grow by a modified endochondral ossification process that involves extensive remodelling of cartilage by osteoclasts. This study identified regenerating antler cartilage as a site of osteoclastogenesis in vivo. An in vitro model was then developed to study antler osteoclast differentiation. Cultured as a high-density micromass, cells from non-mineralised cartilage supported the differentiation of large numbers of osteoclast-like multinucleated cells (MNCs) in the absence of factors normally required for osteoclastogenesis. After 48 h of culture, tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells (osteoclast precursors) were visible, and by day 14 a large number of TRAP-positive MNCs had formed (783+/−200 per well, mean +/− s.e.m., N=4). Reverse transcriptase/polymerase chain reaction (RT-PCR) showed that receptor activator of NF κ B ligand (RANKL) and macrophage colony stimulating factor (M-CSF) mRNAs were expressed in micromass cultures. Antler MNCs have the phenotype of osteoclasts from mammalian bone; they expressed TRAP, vitronectin and calcitonin receptors and, when cultured on dentine, formed F-actin rings and large resorption pits. When cultured on glass, antler MNCs appeared to digest the matrix of the micromass and endocytose type I collagen. Matrix metalloproteinase-9 (MMP-9) may play a role in the resorption of this non-mineralised matrix since it is highly expressed in 100 % of MNCs. In contrast, cathepsin K, another enzyme expressed in osteoclasts from bone, is only highly expressed in resorbing MNCs cultured on dentine. This study identifies the deer antler as a valuable model that can be used to study the differentiation and function of osteoclasts in adult regenerating mineralised tissues.

A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in an acute model of elevated bone turnover in vivo in monkeys

Bone ◽  
2007 ◽  
Vol 40 (1) ◽  
pp. 122-131 ◽  
Author(s):  
S. Kumar ◽  
L. Dare ◽  
J.A. Vasko-Moser ◽  
I.E. James ◽  
S.M. Blake ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Turnover ◽  
Potent Inhibitor ◽  
Cathepsin K

scholarly journals In Vitro Investigations on Optimizing and Nebulization of IVT-mRNA Formulations for Potential Pulmonary-Based Alpha-1-Antitrypsin Deficiency Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1281
Author(s):  
Shan Guan ◽  
Max Darmstädter ◽  
Chuanfei Xu ◽  
Joseph Rosenecker
Keyword(s):  
Epithelial Cells ◽  
Transfection Efficiency ◽  
Genetic Diseases ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Significant Toxicity ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

In vitro-transcribed (IVT) mRNA has come into focus in recent years as a potential therapeutic approach for the treatment of genetic diseases. The nebulized formulations of IVT-mRNA-encoding alpha-1-antitrypsin (A1AT-mRNA) would be a highly acceptable and tolerable remedy for the protein replacement therapy for alpha-1-antitrypsin deficiency in the future. Here we show that lipoplexes containing A1AT-mRNA prepared in optimum conditions could successfully transfect human bronchial epithelial cells without significant toxicity. A reduction in transfection efficiency was observed for aerosolized lipoplexes that can be partially overcome by increasing the initial number of components. A1AT produced from cells transfected by nebulized A1AT-mRNA lipoplexes is functional and could successfully inhibit the enzyme activity of trypsin as well as elastase. Our data indicate that aerosolization of A1AT-mRNA therapy constitutes a potentially powerful means to transfect airway epithelial cells with the purpose of producing functional A1AT, while bringing along the unique advantages of IVT-mRNA.

scholarly journals HIV infection is associated with reduced serum alpha-1-antitrypsin concentrations

2010 ◽  
Vol 33 (6) ◽  
pp. 384 ◽  
Author(s):  
Courtney L Bryan ◽  
K Scott Beard ◽  
Gregory B Pott ◽  
Jeremy Rahkola ◽  
Edward M Gardner ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Fluid Phase ◽  
Cross Sectional Study ◽  
Infected Group ◽  
Cd4 T Cell ◽  
Cross Sectional ◽  
Clinically Significant ◽  
Alpha 1 Antitrypsin

Purpose: Several observations suggest the presence of HIV-suppressive factors in the fluid phase of blood. Alpha-1-antitrypsin (AAT), the most abundant serine protease inhibitor in the circulation, has potent anti-HIV activity in vitro, and may function as an endogenous HIV suppressor. Therefore, we assessed serum AAT concentrations for association with HIV infection. Methods: In this cross-sectional study, serum AAT concentrations were measured in 66 persons with HIV infection and in 45 healthy persons (Controls). In the HIV-infected group, antiretroviral therapy (ART) use was assessed and CD4+ T cell levels and plasma HIV RNA were quantified. Results: Median AAT concentration was significantly lower in the HIV-infected group (1.64 mg/mL) in comparison with Controls (1.94 mg/mL; p=0.001). AAT reduction was most pronounced in the HIV-infected subgroup with CD4+ T cell levels > 200 cells/µL in comparison with Controls (p < 0.01). Serum AAT concentrations < 1.0 mg/mL are clinically significant, and concentrations below this level were identified in 4.5% of the HIV-infected group and in no Control subjects. No association between AAT levels and viral load or use of ART was observed in HIV-infected subjects. Conclusion: The association between reduced serum AAT concentration and HIV infection is consistent with a role for AAT as an endogenous HIV suppressor.

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