Abstract The adaptive immune system can generate distinct classes of responses, but the mechanisms that determine this are poorly understood. In study, we demonstrate different Toll-like receptor (TLR) ligands induce dendritic cell (DC) activation and responses in vivo. Thus, Escherichia coli LPS (TLR-4 stimulus), activates DCs to produce abundant IL-12(p70), little IL-10, stimulates Th1 Tc1 responses. contrast, Pam-3-cys (TLR-2 stimulus) elicits less favors Th2 T cytotoxic 2 (Tc2) These...

Significance Cellular subpopulations in the bone marrow play distinct and unexplored functions regulation of skeleton. A type blood cell that resides termed “osteal macrophage” was found to a role homeostasis by supporting formation mediating parathyroid hormone-dependent regeneration. Furthermore, induction death mature macrophages activated specialized process efferocytosis (clearance dead dying cells), leading microenvironment supported formation.

Tumor cells secrete factors that modulate macrophage activation and polarization into M2 type tumor-associated macrophages, which promote tumor growth, progression, metastasis. The mechanisms mediate this are not clear. Macrophages phagocytic participate in the clearance of apoptotic cells, a process known as efferocytosis. Milk fat globule- EGF factor 8 (MFG-E8) is bridge protein facilitates efferocytosis associated with suppression proinflammatory responses. This study investigated...

During tumor progression, immune system phagocytes continually clear apoptotic cancer cells in a process known as efferocytosis. However, the impact of efferocytosis metastatic growth is unknown. In this study, we observed that macrophage-driven prostate vitro induced expression proinflammatory cytokines such CXCL5 by activating Stat3 and NF-κB(p65) signaling. Administration dimerizer ligand (AP20187) triggered apoptosis 2 vivo syngeneic models bone which apoptosis-inducible were either...

P eriodontal regeneration is a complex process that requires coordinated responses from several cell types within the periodontium. It generally accepted periodontal ligament (PDL) has heterogeneous population, where some of cells may be capable differentiating into either cementoblasts or osteoblasts. Thus, it been hypothesized PDL play role in promoting regeneration. However, definitive evidence to support this concept lacking. Previously, we reported induce biomineralization as determined...

During bone formation, multipotential mesenchymal cells proliferate and differentiate into osteoblasts, subsequently many die because of apoptosis. Evidence suggests that the receptor for parathyroid hormone (PTH) hormone-related protein (PTHrP), PTH-1 (PTH-1R), plays an important role in this process. Multipotential (C3H10T1/2) transfected with normal or mutant PTH-1Rs MC3T3-E1 osteoblastic were used to explore roles PTH, PTHrP, PTH-1R cell viability relative differentiation. Overexpression...

Abstract Expression of parathyroid hormone‐related protein (PTHrP) correlates with prostate cancer skeletal progression; however, the impact cancer‐derived PTHrP on microenvironment and osteoblastic lesions in metastasis has not been completely elucidated. In this study, overexpressing clones were stably established by transfection full length rat cDNA. secretion verified western blotting IRMA assay. cells had higher growth rates vitro , generated larger tumors when inoculated subcutaneously...

Apoptosis occurs at an extraordinary rate in the human body and effective clearance of dead cells (efferocytosis) is necessary to maintain homeostasis promote healing, yet contribution impact this process bone unclear. Bone formation requires that marrow stromal (BMSCs) differentiate into osteoblasts which direct matrix either become osteocytes, lining cells, or undergo apoptosis. A series experiments were performed identify regulators consequences macrophage efferocytosis apoptotic BMSCs...

PTH is an anabolic agent used to treat osteoporosis, but its mechanisms of action are unclear. This study elucidated target cells and for actions in mice during bone growth. Mice with c-fos ablation osteopetrotic lack response PTH. In this study, there were no alterations PTH-regulated osteoblast differentiation or proliferation vitro from -/- compared +/+; hence, the impact osteoclastic was further investigated. A novel transplant model rescue defect ablation. Vertebral bodies (vossicles)...

Abstract PTH has anabolic and catabolic actions in bone that are not clearly understood. The protooncogene c-fos other activating protein 1 family members critical transcriptional mediators bone, is up-regulated by PTH. purpose of this study was to examine the mechanisms role PTH-mediated bone. Mice with ablation (−/−) their wild-type (+/+) heterozygous (+/−) littermates were administered for 17 d. +/+ mice had increased femoral mineral density (BMD), whereas −/− reduced BMD after treatment....

PTHrP induced a proliferative cyclin D1 activation in low-density osteoblastic cells. The process was PKA and MAPK dependent involved both AP-1 CRE sites. In ectopic ossicles generated from implanted bone marrow stromal cells, PTH upregulated after acute or intermittent anabolic treatment. These data suggest positive role of the cell cycle early osteoblasts.The mechanisms underlying actions its related protein (PTHrP) osteoblast proliferation, differentiation, remodeling remain unclear....

Background: Parathyroid hormone‐related protein (PTHrP) promotes osteoclastogenesis by inhibiting expression of osteoprotegerin (OPG), a decoy receptor for the activator nuclear factor kappa B (RANK), and enhancing production RANK ligand (RANKL) osteoblasts. However, little is known regarding role PTHrP in regulating cementoblast‐mediated osteoclastogenesis. Methods: This study determined impact on using: 1) OCCM‐30 (immortalized murine cementoblasts), 2) RAW 264.7 cells (murine myeloid...

Abstract A number of cancers predominantly metastasize to bone, due its complex microenvironment and multiple types constitutive cells. Prostate cancer especially has been shown localize preferentially bones with higher marrow cellularity. Using an experimental prostate metastasis model, we investigated the effects cyclophosphamide, a bone marrow–suppressive chemotherapeutic drug, on development growth metastatic tumors in bone. Priming murine host cyclophosphamide before intracardiac tumor...

In the tumor microenvironment, CD11b(+)Gr1(+) bone marrow-derived cells are a predominant source of protumorigenic factors such as matrix metalloproteinases (MMP), but how distal tumors regulate these in marrow is unclear. Here we addressed hypothesis that parathyroid hormone-related protein (PTHrP) potentiates prostate hosts. two xenograft models cancer, levels tumor-derived PTHrP correlated with cell recruitment and microvessel density tissue, evidence for mediation cell-derived MMP-9 not...

// Fabiana N. Soki 1 , Sun Wook Cho 2 Yeo Won Kim Jacqueline D. Jones Serk In Park 3,4 Amy J. Koh Payam Entezami Stephanie Daignault-Newton 5 Kenneth Pienta 6 Hernan Roca and Laurie K. McCauley 1,7 Department of Periodontics Oral Medicine, University Michigan School Dentistry, Ann Arbor, MI, USA Internal National Medical Center, Jung-gu, Seoul, Korea 3 Vanderbilt Nashville, TN, 4 Biochemistry Molecular Biology, College Center for Cancer Biostatistics, Michigan, The James Buchanan Brady...

Macrophages play a dual role in regulating tumor progression. They can either reduce growth by secreting antitumorigenic factors or promote progression variety of soluble factors. The purpose this study was to define the monocyte/macrophage population prevalent skeletal tumors, explore mechanism employed supporting prostate cancer (PCa) metastasis, and examine novel therapeutic target. Phagocytic CD68+ cells were found correlate with Gleason score human PCa samples, M2-like macrophages...

Abstract Apoptosis and efficient efferocytosis are integral to growth, development, homeostasis. The heterogeneity of these mechanisms in different cells across distinct tissues renders it difficult develop broadly applicable vivo technologies. Here, we introduced a novel inducible caspase-9 (iCasp9) mouse model which allowed targeted cell apoptosis further facilitated investigation concomitant efferocytosis. We generated iCasp9 +/+ mice with conditional expression chemically protein that is...

Abstract Apoptosis is crucial for tissue homeostasis and organ development. In bone, apoptosis recognized to be a main fate of osteoblasts, yet the relevance this process remains underexplored. Using our murine model with inducible Caspase 9, enzyme that initiates intrinsic apoptosis, we triggered in proportion mature osteocalcin (OCN + ) osteoblasts investigated impact on postnatal bone Osteoblast stimulated efferocytosis by osteal macrophages. A five-week stimulation OCN osteoblast...

The temporal sequence of PTH/PTHrP receptor mRNA, binding, biologic activity, and its dependence on matrix synthesis was determined using MC3T3-E1 preosteoblast-like cells primary rat calvarial in vitro. Osteoblastic were induced to differentiate form mineralized nodules with the addition ascorbic acid β-glycerophosphate, samples collected from 0–26 days culture. DNA levels as by fluorometric analysis increased 12- 17-fold during collection period for both respectively. Steady state mRNA...

Abstract Bone marrow macrophages stimulate skeletal wound repair and osteoblastic bone formation by poorly defined mechanisms. Specialized proresolving mediators of inflammation drive macrophage efferocytosis (phagocytosis apoptotic cells) resolution, but little is known regarding this process in the marrow. In study, metabololipidomic profiling via liquid chromatography mass spectrometry revealed higher levels specialized relative to spleen. The endocrine anabolic agent parathyroid hormone...

Abstract TGFβ has opposing effects on osteoblasts which are thought to be differentiation stage dependent; however, little is known concerning the of osteoblastic characteristics at different stages maturation. The purpose this study was characterize pattern mRNA expression for PTH/PTHrP receptor during normal in vitro, and evaluate TGFβ1 osteocalcin (OCN) steady-state differentiation. MC3T3-E1 preosteoblasts were plated low density induced differentiate with ascorbic acid...

Parathyroid hormone-related protein (PTHrP) regulates proliferation and differentiation of osteoblastic cells via binding to the parathyroid hormone receptor (PTH-1R). The cAMP-dependent kinase A pathway governs majority these effects, but recent evidence also implicates MAPK pathway. MC3T3-E1 subclone 4 (MC4) were treated with inhibitor U0126 PTHrP. In differentiated MC4 cells, osteocalcin bone sialoprotein gene expression both down-regulated by PTHrP inhibition PTHrP-mediated...