scholarly journals Mycobacterium tuberculosis Chaperonin 10 Stimulates Bone Resorption: A Potential Contributory Factor in Pott's Disease

1997 ◽  
Vol 186 (8) ◽  
pp. 1241-1246 ◽  
Author(s):  
Sajeda Meghji ◽  
Peter A. White ◽  
Sean P. Nair ◽  
Krisanavane Reddi ◽  
Kyle Heron ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bone Resorption ◽  
Spinal Tuberculosis ◽  
Bone Diseases ◽  
Contributory Factor ◽  
Pott’S Disease ◽  
Chaperonin 10 ◽  
Cpn 10 ◽  
First Time ◽  
Bone Resorbing Activity

Pott's disease (spinal tuberculosis), a condition characterized by massive resorption of the spinal vertebrae, is one of the most striking pathologies resulting from local infection with Mycobacterium tuberculosis (Mt; Boachie-Adjei, O., and R.G. Squillante. 1996. Orthop. Clin. North Am. 27:95–103). The pathogenesis of Pott's disease is not established. Here we report for the first time that a protein, identified by a monoclonal antibody to be the Mt heat shock protein (Baird, P.N., L.M. Hall, and A.R.M. Coates. 1989. J. Gen. Microbiol. 135:931–939) chaperonin (cpn) 10, is responsible for the osteolytic activity of this bacterium. Recombinant Mt cpn10 is a potent stimulator of bone resorption in bone explant cultures and induces osteoclast recruitment, while inhibiting the proliferation of an osteoblast bone–forming cell line. Furthermore, we have found that synthetic peptides corresponding to sequences within the flexible loop and sequence 65–70 of Mt cpn10 may comprise a single conformational unit which encompasses its potent bone-resorbing activity. Our findings suggest that Mt cpn10 may be a valuable pharmacological target for the clinical therapy of vertebral tuberculosis and possibly other bone diseases.

scholarly journals Mycobacterium tuberculosis Chaperonin 10 Heptamers Self-Associate through Their Biologically Active Loops

2003 ◽  
Vol 185 (14) ◽  
pp. 4172-4185 ◽  
Author(s):  
Michael M. Roberts ◽  
Alun R. Coker ◽  
Gianluca Fossati ◽  
Paolo Mascagni ◽  
Anthony R. M. Coates ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bone Resorption ◽  
Structural Features ◽  
Biologically Active ◽  
Protein Subunit ◽  
Common Receptor ◽  
Loop Sequence ◽  
Chaperonin 10 ◽  
Hydrophilic Residues

ABSTRACT The crystal structure of Mycobacterium tuberculosis chaperonin 10 (cpn10Mt) has been determined to a resolution of 2.8 Å. Two dome-shaped cpn10Mt heptamers complex through loops at their bases to form a tetradecamer with 72 symmetry and a spherical cage-like structure. The hollow interior enclosed by the tetradecamer is lined with hydrophilic residues and has dimensions of 30 Å perpendicular to and 60 Å along the sevenfold axis. Tetradecameric cpn10Mt has also been observed in solution by dynamic light scattering. Through its base loop sequence cpn10Mt is known to be the agent in the bacterium responsible for bone resorption and for the contribution towards its strong T-cell immunogenicity. Superimposition of the cpn10Mt sequences 26 to 32 and 66 to 72 and E. coli GroES 25 to 31 associated with bone resorption activity shows them to have similar conformations and structural features, suggesting that there may be a common receptor for the bone resorption sequences. The base loops of cpn10s in general also attach to the corresponding chaperonin 60 (cpn60) to enclose unfolded protein and to facilitate its correct folding in vivo. Electron density corresponding to a partially disordered protein subunit appears encapsulated within the interior dome cavity of each heptamer. This suggests that the binding of substrates to cpn10 is possible in the absence of cpn60.

scholarly journals A case of not just Pott’s disease

2021 ◽  
Vol 8 ◽  
pp. 204993612110414
Author(s):  
William Greene ◽  
Martin Prager ◽  
Marlin Richardson
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Epidural Abscess ◽  
Spinal Tuberculosis ◽  
Vertebral Osteomyelitis ◽  
Streptococcus Anginosus ◽  
Pott’S Disease ◽  
Developed World

Spinal tuberculosis (TB) is a rare cause of vertebral osteomyelitis in the developed world. Co-infections with other microorganisms are seldom reported in the literature. Here we report a case of Mycobacterium tuberculosis and Streptococcus anginosus causing acute on chronic vertebral osteomyelitis with an epidural abscess.

Co-purification of bone resorbing activity and adenylate cyclase stimulating activity from human tumours associated with the humoral hypercalcaemia of malignancy

1987 ◽  
Vol 114 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Chohei Shigeno ◽  
Itsuo Yamamoto ◽  
Shegiharu Dokoh ◽  
Megumu Hino ◽  
Jun Aoki ◽  
...  
Keyword(s):  
Bone Resorption ◽  
High Performance ◽  
Basic Protein ◽  
Gel Filtration ◽  
Exchange Chromatography ◽  
Protein Factor ◽  
Human Tumours ◽  
Acid Stable ◽  
Bone Resorbing Activity

Abstract. We have partially purified a tumour factor capable of stimulating both bone resorption in vitro and cAMP accumulation in osteoblastic ROS 17/2 cells from three human tumours associated with humoral hypercalcaemia of malignancy. Purification of tumour factor by sequential acid urea extraction, gel filtration and cation-exchange chromatography, reverse-phase high performance liquid chromatography followed by analytical isoelectric focussing provided a basic protein (pI > 9.3) with a molecular weight of approximately 13 000 as a major component of the final preparation which retained both the two bioactivities. Bone resorbing activity and cAMP-increasing activity in purified factor correlated with each other. cAMP-increasing activity of the factor was heat- and acid-stable, but sensitive to alkaline ambient pH. Treatment with trypsin destroyed cAMP-increasing activity of the factor. Synthetic parathyroid hormone (PTH) antagonist, human PTH-(3– 34) completely inhibited the cAMP-increasing activity of the factor. The results suggest that this protein factor, having its effects on both osteoclastic and osteoblastic functions, may be involved in development of enhanced bone resorption in some patients with humoral hypercalcaemia of malignancy.

Synthetic Aspects and First-time Assessment of 2-amino-1,3-selenazoles Against Mycobacterium tuberculosis

2018 ◽  
Vol 15 (11) ◽  
pp. 1224-1229 ◽  
Author(s):  
Victor Facchinetti ◽  
Marcus V.N. De Souza ◽  
Ana C.S. Nery ◽  
Stephane L. Calixto ◽  
Juliana T. Granato ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
First Time ◽  
Time Assessment

scholarly journals Rifampicin-Resistant Disseminated Tuberculosis in an Immunocompetent Adolescent Male Presenting with Retropharyngeal Abscess and Spinal Involvement

2021 ◽  
Author(s):  
Arghya Das ◽  
Vineeta Gupta ◽  
Shampa Anupurba
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Effective Treatment ◽  
Spinal Tuberculosis ◽  
Clinical Specimen ◽  
Retropharyngeal Abscess ◽  
Adolescent Male ◽  
Irreversible Damage ◽  
Disseminated Tuberculosis ◽  
Rare Manifestation ◽  
Microbiological Confirmation

AbstractRetropharyngeal abscess is a rare manifestation in spinal tuberculosis. Early clinical diagnosis followed by microbiological confirmation and effective treatment is crucial to avoid irreversible damage to the spine. Here, we report a case of disseminated tuberculosis in an immunocompetent adolescent male who presented with retropharyngeal abscess, multifocal involvement of the spine, and skin tuberculids. Xpert MTB/RIF assay in this patient facilitated early lifesaving treatment by detecting rifampicin-resistant Mycobacterium tuberculosis (MTB) in the clinical specimen.

scholarly journals Solvent-Free Processing of Drug-Loaded Poly(ε-Caprolactone) Scaffolds with Tunable Macroporosity by Combination of Supercritical Foaming and Thermal Porogen Leaching

Polymers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 159
Author(s):  
Víctor Santos-Rosales ◽  
Inés Ardao ◽  
Leticia Goimil ◽  
Jose Luis Gomez-Amoza ◽  
Carlos A. García-González
Keyword(s):  
Bone Repair ◽  
Drug Loading ◽  
Ammonium Bicarbonate ◽  
Bone Diseases ◽  
Solvent Free ◽  
Bone Integration ◽  
Bioactive Agents ◽  
First Time ◽  
Supercritical Foaming ◽  
Foaming Technology

Demand of scaffolds for hard tissue repair increases due to a higher incidence of fractures related to accidents and bone-diseases that are linked to the ageing of the population. Namely, scaffolds loaded with bioactive agents can facilitate the bone repair by favoring the bone integration and avoiding post-grafting complications. Supercritical (sc-)foaming technology emerges as a unique solvent-free approach for the processing of drug-loadenu7d scaffolds at high incorporation yields. In this work, medicated poly(ε-caprolactone) (PCL) scaffolds were prepared by sc-foaming coupled with a leaching process to overcome problems of pore size tuning of the sc-foaming technique. The removal of the solid porogen (BA, ammonium bicarbonate) was carried out by a thermal leaching taking place at 37 °C and in the absence of solvents for the first time. Macroporous scaffolds with dual porosity (50–100 µm and 200–400 µm ranges) were obtained and with a porous structure directly dependent on the porogen content used. The processing of ketoprofen-loaded scaffolds using BA porogen resulted in drug loading yields close to 100% and influenced its release profile from the PCL matrix to a relevant clinical scenario. A novel solvent-free strategy has been set to integrate the incorporation of solid porogens in the sc-foaming of medicated scaffolds.

scholarly journals Inhibitory Effect of LGS and ODE Isolated from the Twigs of Syringa oblata subsp. dilatata on RANKL-Induced Osteoclastogenesis in Macrophage Cells

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1779
Author(s):  
Ga-Ram Kim ◽  
Eun-Nam Kim ◽  
Kyoung Jin Park ◽  
Ki Hyun Kim ◽  
Gil-Saeng Jeong
Keyword(s):  
Protein Kinase ◽  
Bone Resorption ◽  
Signaling Pathways ◽  
Natural Product ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Pivotal Role ◽  
Nuclear Factor ◽  
Bone Homeostasis ◽  
Nuclear Factor Kappa

Osteoblasts and osteoclasts play a pivotal role in maintaining bone homeostasis, of which excessive bone resorption by osteoclasts can cause osteoporosis and various bone diseases. However, current osteoporosis treatments have many side effects, and research on new treatments that can replace these treatments is ongoing. Therefore, in this study, the roles of ligustroside (LGS) and oleoside dimethylester (ODE), a natural product-derived compound isolated from Syringa oblata subsp. dilatata as a novel, natural product-derived osteoporosis treatments were investigated. In the results of this study, LGS and ODE inhibited the differentiation of receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced RAW264.7 cells into osteoclasts without cytotoxicity, and down-regulated the activity of TRAP, a specific biomarker of osteoclasts. In addition, it inhibited bone resorption and actin ring formation, which are important functions and features of osteoclasts. Also, the effects of LGS and ODE on the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and phosphoinositide 3-kinases (PI3K)/ protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling pathways that play important roles in osteoclast differentiation were evaluated. In the results, LGS and ODE downregulated the phosphorylation of RANKL-induced MAPK and PI3K/Akt/mTOR proteins in a concentration-dependent manner, translocation of NF-κB into the nucleus was inhibited. As a result, the compounds LGS and ODE isolated from S. oblate subsp. dilatata effectively regulated the differentiation of RANKL-induced osteoclasts and inhibited the phosphorylation of signaling pathways that play a pivotal role in osteoclast differentiation. Therefore, these results suggest the possibility of LGS and ODE as new natural product treatments for bone diseases caused by excessive osteoclasts.

scholarly journals Capsaicin, a TRPV1 Ligand, Suppresses Bone Resorption by Inhibiting the Prostaglandin E Production of Osteoblasts, and Attenuates the Inflammatory Bone Loss Induced by Lipopolysaccharide

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Megumi Kobayashi ◽  
Kenta Watanabe ◽  
Satoshi Yokoyama ◽  
Chiho Matsumoto ◽  
Michiko Hirata ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Transient Receptor Potential ◽  
Interleukin 1 ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Prostaglandin E ◽  
Transient Receptor Potential Vanilloid ◽  
Cox 2

Capsaicin, a transient receptor potential vanilloid type 1 (TRPV1) ligand, regulates nerve-related pain-sensitive signals, inflammation, and cancer growth. Capsaicin suppresses interleukin-1-induced osteoclast differentiation, but its roles in bone tissues and bone diseases are not known. This study examined the effects of capsaicin on inflammatory bone resorption and prostaglandin E (PGE) production induced by lipopolysaccharide (LPS) in vitro and on bone mass in LPS-treated mice in vivo. Capsaicin suppressed osteoclast formation, bone resorption, and PGE production induced by LPS in vitro. Capsaicin suppressed the expression of cyclooxygenase-2 (COX-2) and membrane-bound PGE synthase-1 (mPGES-1) mRNAs and PGE production induced by LPS in osteoblasts. Capsaicin may suppress PGE production by inhibiting the expression of COX-2 and mPGES-1 in osteoblasts and LPS-induced bone resorption by TRPV1 signals because osteoblasts express TRPV1. LPS treatment markedly induced bone loss in the femur in mice, and capsaicin significantly restored the inflammatory bone loss induced by LPS in mice. TRPV1 ligands like capsaicin may therefore be potentially useful as clinical drugs targeting bone diseases associated with inflammatory bone resorption.

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