A5062332683- Bone health and treatments
- Bone Metabolism and Diseases
- Biomarkers in Disease Mechanisms
- Multiple Myeloma Research and Treatments
- Cancer Diagnosis and Treatment
- Fibroblast Growth Factor Research
- Cell Adhesion Molecules Research
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Vitamin D Research Studies
- Cytokine Signaling Pathways and Interactions
- Bone and Dental Protein Studies
- Alkaline Phosphatase Research Studies
- Histone Deacetylase Inhibitors Research
- S100 Proteins and Annexins
- Protease and Inhibitor Mechanisms
- Bone and Joint Diseases
- Periodontal Regeneration and Treatments
- Hepatitis B Virus Studies
- Estrogen and related hormone effects
- Dental Implant Techniques and Outcomes
- Inflammatory mediators and NSAID effects
- Blood disorders and treatments
- NF-κB Signaling Pathways
- Bone Tumor Diagnosis and Treatments
Indiana University – Purdue University Indianapolis
2015-2024
Indiana University School of Medicine
2013-2023
Indiana University Indianapolis
2022
University of Indianapolis
2022
University of Pittsburgh Medical Center
2004-2012
University of Pittsburgh
2004-2011
VA Pittsburgh Healthcare System
2006-2011
Palmetto Hematology Oncology
1993-2010
UPMC Hillman Cancer Center
2005-2009
Charité - Universitätsmedizin Berlin
2005
IL-6 enhances the differentiation of pluripotent hematopoietic stem cells but predominantly affects in granulocyte-macrophage lineage. We have previously shown that multinucleated (MNC) with many features osteoclast phenotype form long term human marrow cultures. Addition rhIL-6 (10 to 100 pg/ml) these cultures significantly increased MNC formation, greater than 80% expressing an Ag cross-reacts mAb 23c6. This antibody preferentially binds osteoclasts. did not enhance formation treated 1,25...
Pagetic osteoclasts are greatly increased in number and size have numbers of nuclei per cell compared to normal osteoclasts. The mechanisms responsible for enhanced osteoclast formation Paget's disease unknown. We used our recently described model system pagetic evaluate culture media conditioned by these atypical multinucleated cells (MNC) determine if produce an autocrine or paracrine factor that enhances formation. Conditioned from long-term bone marrow cultures patients with stimulated...
Prostaglandin (PG) E,, known as a bone-resorption factor, was released predominant arachidonate metabolite in the culture medium of an osteoblastic cell line cloned from mouse calvaria (MC3T3-El).Epidermal growth factor (EGF) (10 ng/ml) prominently enhanced endogenous PGE, synthesis, requiring simultaneous presence unidentified factor(s) contained bovine serum.PGE2 synthesis increased after lag phase for 1-2 h and reached maximum level at about 3 EGF addition.EGF-stimulated almost completely...
Paget's disease is characterized by highly localized areas of increased osteoclast (OCL) activity. This suggests that the microenvironment in pagetic lesions osteoclastogenic, or OCL precursors these are hyperresponsive to osteoclastogenic factors (or both). To examine possibilities, we compared RANK ligand (RANKL) mRNA expression a marrow stromal cell line developed from lesion (PSV10) with normal (Saka), and samples affected bones patients marrow. RANKL was PSV10 cells Saka marrow, also...
Osteoclasts (OCLs) in Paget's disease are markedly increased number and size, have numbers of nuclei per multinucleated cell, demonstrate resorption capacity sensitivity to 1,25-(OH)2D3, the active form vitamin D. These cells also contain nuclear inclusions, reminiscent those seen paramyxovirus-infected cells, which cross-react with antibodies measles virus nucleocapsid (MVNP) antigen. To elucidate role MV abnormal OCL phenotype disease, we transduced normal precursors retroviral vectors...
Paget disease is the most exaggerated example of abnormal bone remodeling, with primary cellular abnormality in osteoclast. Mutations p62 (sequestosome 1) gene occur one-third patients familial and a minority sporadic disease, P392L amino acid substitution being commonly observed mutation. However, it unknown how p62(P392L) mutation contributes to development this disease. To determine effects expression on osteoclasts vitro vivo, we introduced either or WT into normal osteoclast precursors...
Abstract The effect of prostaglandin E 2 (PGE ) on osteoblastic cell proliferation was investigated using clone MC3T3‐E1 cells cultured in serum‐free medium. PGE at μg/ml increased the number by days after its addition. raised level DNA synthesis a dose‐related fashion constant lag time, maximal being 2–10 and about fourfold over that control 36 hr However, low doses (below 0.2 μg/ml), rather depressed synthesis. Isobutyl methylxanthine counteracted stimulation , forskolin synthesis, which...
Abstract Recently we have adapted human long-term bone marrow cultures to form multinucleated cells (MNC) that express the osteoclast phenotype and used semisolid culture techniques identify early (bipotent) late (unipotent) mononuclear precursors for these MNC. The precursor can both osteoclast-like MNC macrophage polykaryons; forms only In this study examined effects of osteotropic hormones cytokines formation from highly purified populations or cells. expressing were identified by their...
1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] was examined for a possible stimulative effect on osteoblastic MC3T3-E1 cells. During the early period of culture, 1,25-(OH)2D3 had effect. growth phase, however, steroid little either protein or DNA content cultures. increased bone-liverkidney-type alkaline phosphatase activity in dose-related manner up to concentration 5 pg/ml; increase 2.2-fold over control value. Studies actinomycin D cycloheximide treatment indicated that vitamin may enhance de...
Activating transcription factor 4 (ATF4) is a critical for osteoblast (OBL) function and bone formation; however, direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using Trap promoter or through deletion Atf4 mice. differentiation was drastically decreased Atf4–/– marrow monocyte (BMM) cultures bones. Coculture BMMs with WT OBLs high concentration RANKL failed restore defect. Conversely, Trap-Atf4-tg mice displayed severe...
Abstract We targeted the MVNP gene to OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar those found Paget's patients. results show that persistent expression of can induce pagetic-like vivo. Introduction: disease (PD) is second most common disease. Both genetic viral factors have been implicated its pathogenesis, but their exact roles vivo are unclear. previously reported transfection normal human osteoclast (OCL) precursors with measles virus...
Paget's disease of bone (PDB) is the second most common and characterized by focal lesions which contain large numbers abnormal osteoclasts (OCLs) very active normal osteoblasts in a highly osteoclastogenic marrow microenvironment. The etiology PDB not well understood both environmental genetic causes have been implicated its pathogenesis. Mutations SQSTM1/p62 gene identified up to 30% patients. To determine if p62 mutation sufficient induce PDB, we generated mice harboring causing P-to-L...
The effects of prostaglandins (PGs) on the induction alkaline phosphatase (ALP) were investigated in osteoblastic clone MC3T3-E1 cells cultured serum-free medium. Prostaglandin E2 (PGE2) stimulated ALP activity a dose-dependent fashion with maximal effect which was about twice that control at concentrations 100-500 ng/ml. Actinomycin D and cycloheximide inhibited stimulative PGE2 cells. PGE2-induced native ALPs same type as adult mouse calvaria, being heat-labile, L-homoarginine-...
Multiple myeloma (MM) is an incurable malignancy of plasma cells. To identify targets for MM immunotherapy, we develop integrated pipeline based on mass spectrometry analysis seven cell lines and RNA sequencing (RNA-seq) from 900+ patients. Starting 4,000+ candidates, the most highly expressed surface proteins. We annotate candidate protein expression in many healthy tissues validate promising 30+ patient samples with relapsed/refractory MM, as well primary hematopoietic stem cells T by flow...
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