Osteoclast, a huge coenocytes,originates from mononuclear macrophages or monocytic series hematopoietic precursor cell, plays an important role in the progree of bone resorption. Formation and abnormal activity of osteoclast may cause osteoprosis, rheumatoid arthritis and aseptic loosening after arthroplasty. Therefore, osteoclast is the target for treating these disease. At present, a lot of study on formation of osteoclast were reported, but the study on how to identify and degradation of bone tissue is not yet reported. Bone mineral are seen as important component of identifing osteoclast, and the research suggested that bone matrix is not the essential ingredients of activiting osteoclast, petri dish covered by vitronectin also can make osteoclast occure certain form of bone resorption, vitronectin plays an significant role in activiting osteoclast. Otherwise, the research found that swallowing and secretion of bone matrix degradation products is benefit for differentiation of osteoclast and maintain of function, and this may be therapeutic target for treatment of musculoskeletal disorders.
Animals ; Bone Matrix ; metabolism ; Bone Resorption ; Humans ; Osteoclasts ; physiology

The physiological reconstruction of bone is strictly dependent on bone resorption. Bone resorption is believed to be a complicated molecular reaction process that occurs in the microcircumstance of bone tissue. A lot of enzymes and factors take part in this process, yet there are not enough data with reference to the activation of osteoclast, resorption of bone matrix, regulation of bone resorption. In this paper we review the importance of matrix metalloproteinases (MMPs) in transfer of osteoclast and degradation of bone matrix, and the function of receptor activator of NF-kappaB-ligand (RANKL) and osteoprotegerin (OPG) in regulation of bone resorption.
Bone Resorption ; Humans ; Matrix Metalloproteinases ; metabolism ; Osteoclasts ; physiology ; Osteoprotegerin ; physiology ; RANK Ligand ; physiology

The bone remodeling process in response to orthodontic forces requires the activity of osteoclasts to allow teeth to move in the direction of the force applied. Receptor activator of nuclear factor-κB ligand (RANKL) is essential for this process although its cellular source in response to orthodontic forces has not been determined. Orthodontic tooth movement is considered to be an aseptic inflammatory process that is stimulated by leukocytes including T and B lymphocytes which are presumed to stimulate bone resorption. We determined whether periodontal ligament and bone lining cells were an essential source of RANKL by tamoxifen induced deletion of RANKL in which Cre recombinase was driven by a 3.2 kb reporter element of the Col1α1 gene in experimental mice (Col1α1.CreER.RANKL) and compared results with littermate controls (Col1α1.CreER.RANKL). By examination of Col1α1.CreER.ROSA26 reporter mice we showed tissue specificity of tamoxifen induced Cre recombinase predominantly in the periodontal ligament and bone lining cells. Surprisingly we found that most of the orthodontic tooth movement and formation of osteoclasts was blocked in the experimental mice, which also had a reduced periodontal ligament space. Thus, we demonstrate for the first time that RANKL produced by periodontal ligament and bone lining cells provide the major driving force for tooth movement and osteoclastogenesis in response to orthodontic forces.
Animals ; Bone Remodeling ; physiology ; Mice ; Mice, Transgenic ; Osteoclasts ; physiology ; Periodontal Ligament ; metabolism ; RANK Ligand ; metabolism ; Tamoxifen ; pharmacology ; Tooth Movement Techniques

OBJECTIVETo study the expression of dentin matrix protein 1 (DMP1) and osteoclast in callus at different healing period of mandibular fracture in a adult Wistar rat model.

METHODSThe mandibular fracture model of Wistar rats at the left mandibular ramus was established. The callus in the fractured site and the normal mandible were amputated at the 5th, 7th, 14th and 21st day after the fracture. HE staining was used to observe the condition of fracture healing and TRAP staining used to observe the activation of osteoclast. The expression of DMP1 was detected in the callus by using immunohistochemical method.

RESULTSThe number of osteoclasts reached a peak from the 14th to 21st day. The expression of DMP1 became very active from the 7th to 14th day.

CONCLUSIONSThe expression of DMP1 and osteoclast during fracture healing exhibited time effect.

Animals ; Disease Models, Animal ; Extracellular Matrix Proteins ; metabolism ; Fracture Healing ; physiology ; Mandible ; metabolism ; Mandibular Fractures ; metabolism ; physiopathology ; Osteoclasts ; physiology ; Phosphoproteins ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo investigate the osteoblast-like functional characteristics exhibited by human periodontal ligament cells (hPDLCs) under mechanical force.

METHODSHuman PDLCs cultured in vitro were stretched by mechanical force. Radioimmunoassay (RIA) was used to measure the expression of secreting alkaline phosphotase (ALP) and osteocalcin (OCN). The non-secreting ALP, OCN and osteopontin (OPN) in cells were determined by immunohistochemistry.

RESULTSIt exhibited increasing of ALP secreted into conditional media, and in the 24 hour period there were two peaks which appeared at the 2nd and 4th hour and the 24th hour (P < 0.01). While in the late of the 24 hours, expression of OCN in conditional media increased (P < 0.05).

CONCLUSIONMechanical force induces hPDLCs to differentiate into functional osteoblast-like cells and plays a role in bone remodeling.

Alkaline Phosphatase ; metabolism ; Cells, Cultured ; Humans ; Osteocalcin ; analysis ; Osteoclasts ; physiology ; Osteopontin ; Periodontal Ligament ; cytology ; Sialoglycoproteins ; analysis ; Stress, Mechanical

The OPG/RANKL/RANK system plays an important role in osteoclastogenesis and represents a great progress in bone biology. RANKL, which expresses on the surface of osteoblast/stromal cells and activated T cells, binds to RANK on the osteoclastic precursors or mature osteoclasts, and promotes osteoclastogenesis and bone resorption. While osteoprotegerin (OPG), which is expressed by osteoblasts/stromal cells, strongly inhibits bone resorption by binding to its ligand RANKL and thereby blocks the interaction between BANKL and RANK. A number of cytokines and hormones exert their effects on bone metabolism by regulating the OPG/RANKL ratio in the bone marrow microenvironment. RANK is also expressed on mammary epithelial cells and RANKL expression in these cells is induced by pregnancy hormones, RANKL and RANK are essential for the formation of the lactating mammary gland and the transmission of maternal calcium to neonates in mammalian species. Modulation of these systems provides a unique opportunity to develop novel therapeutics to inhibit bone loss in osteoporosis, rheumatoid arthritis, and bone metastasis of cancer. Further research should be focused on the cooperation of OPG/RANKL/RANK system with other signal pathways and the interactions among bone remodeling, immune system and endocrinology system. Currently, the development of OPG analogues or compounds which may stimulate OPG expression is becoming an attractive industry which may be profitable to both patients and manufacturers.
Animals ; Bone Resorption ; immunology ; metabolism ; Humans ; Osteoclasts ; cytology ; metabolism ; pathology ; Osteogenesis ; drug effects ; genetics ; immunology ; Osteoprotegerin ; metabolism ; physiology ; RANK Ligand ; metabolism ; physiology ; Receptor Activator of Nuclear Factor-kappa B ; metabolism ; pharmacology ; physiology ; T-Lymphocytes ; drug effects ; immunology

PURPOSETo investigate the influence of the same mechanical loading on osteogenesis and osteoclastogenesis in vitro.

METHODSPrimary osteoblasts, bone marrow-derived mesenchymal stem cells (BMSCs, cultured in osteoinductive medium) and RAW264.7 cells cultured in osteoclast inductive medium were all subjected to a 1000 μstrain (μs) at 1 Hz cyclic mechanical stretch for 30 min (twice a day).

RESULTSAfter mechanical stimulation, the alkaline phosphatase (ALP) activity, osteocalcin protein level of the osteoblasts and BMSCs were all enhanced, and the mRNA levels of ALP and collagen type I increased. Additionally, extracellular-deposited calcium of both osteoblasts and BMSCs increased. At the same time, the activity of secreted tartrate-resistant acid phosphatase, the number of tartrate-resistant acid phosphatase-positive multinucleated cells, matrix metalloproteinase-9 protein levels of RAW264.7 cells and the extracellular calcium solvency all decreased.

CONCLUSIONThe results demonstrated that 1000 μs cyclic mechanical loading enhanced osteoblasts activity, promoted osteoblastic differentiation of BMSCs and restrained osteoclastogenesis of RAW264.7 cells in vitro.

Animals ; Biomechanical Phenomena ; Cell Differentiation ; Cells, Cultured ; Mice ; Mice, Inbred C57BL ; Osteoblasts ; cytology ; Osteoclasts ; physiology ; Osteogenesis ; physiology ; Tartrate-Resistant Acid Phosphatase ; metabolism

In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections. Infection-related bone destruction incorporates pathogens and iatrogenic factors in the process of bone resorption dominated by the skeletal and immune systems. The development of bone immunology has established a bridge of communication between the skeletal system and the immune system. Exploring the effects of pathogens, skeletal systems, immune systems, and antibacterials on bone repair in infectious conditions can help improve the treatment of these diseases.
Anti-Bacterial Agents/administration & dosage* ; Bone and Bones/metabolism* ; Cellular Microenvironment ; Humans ; Immune System/immunology* ; Lymphocyte Subsets/immunology* ; Osteitis/microbiology* ; Osteoblasts/physiology* ; Osteoclasts/physiology* ; Staphylococcal Infections

Animals ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Differentiation ; Humans ; Mouth Neoplasms ; metabolism ; pathology ; Oral Medicine ; Osteoblasts ; cytology ; Osteoclasts ; cytology ; Tooth ; metabolism ; Wnt Proteins ; metabolism ; physiology ; Wnt Signaling Pathway ; physiology ; beta Catenin ; metabolism

As a dioxygenase, Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (5hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities.
5-Methylcytosine ; analogs & derivatives ; chemistry ; metabolism ; Animals ; Cell Differentiation ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; DNA-Binding Proteins ; physiology ; Genome ; Genomics ; Mice ; Mice, Knockout ; Osteoclasts ; cytology ; metabolism ; Proto-Oncogene Proteins ; physiology