Mechanical signals control SOX-9, VEGF, and c-Myc expression and cell proliferation during inflammation via integrin-linked kinase, B-Raf, and ERK1/2-dependent signaling in articular chondrocytes.

Introduction: The importance of mechanical signals in normal and inflamed cartilage is well established. Chondrocytes respond to changes in the levels of proinflammatory cytokines and mechanical signals during inflammation. Cytokines like interleukin (IL)-1beta suppress homeostatic mechanisms and inhibit cartilage repair and cell proliferation.

Correlation of tuned aperture computed tomography with conventional computed tomography for evaluation of osseous healing in calvarial defects.

Objective: To compare the diagnostic efficacy of iteratively restored tuned aperture computed tomography (TACT) with conventional computed tomography (CT) for evaluation of osseous healing in induced calvarial defects.

Study Design: Fifty-six calvarial defects in 14 rabbits received 1 of 4 possible treatments: copolymer membranes with and without bone marrow stromal cells (BMSCs), BMSCs alone, or no treatment (control). Healing was measured after 2, 4, and 8 wks as remaining defect areas measured on TACT and CT images.

Biomechanical signals exert sustained attenuation of proinflammatory gene induction in articular chondrocytes.

Objectives: Physical therapies are commonly used for limiting joint inflammation. To gain insight into their mechanisms of actions for optimal usage, we examined persistence of mechanical signals generated by cyclic tensile strain (CTS) in chondrocytes, in vitro. We hypothesized that mechanical signals induce anti-inflammatory and anabolic responses that are sustained over extended periods.

MMP20 active-site mutation in hypomaturation amelogenesis imperfecta.

The Amelogenesis Imperfecta (AI) are a group of clinically and genetically heterogeneous disorders that affect enamel formation. To date, mutations in 4 genes have been reported in various types of AI. Mutations in the genes encoding the 2 enamel proteases, matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4), have each been reported in a single family segregating autosomal-recessive hypomaturation AI.

Anti-inflammatory effects of continuous passive motion on meniscal fibrocartilage.

Motion-based therapies have been applied to promote healing of arthritic joints. The goal of the current study was to determine the early molecular events that are responsible for the beneficial actions of motion-based therapies on meniscal fibrocartilage. Rabbit knees with Antigen-Induced-Arthritis (AIA) were exposed to continuous passive motion (CPM) for 24 or 48 h and compared to immobilized knees.

Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals.

Objective: The mechanisms by which chondrocytes convert biomechanical signals into intracellular biochemical events are not well understood. In this study, we sought to determine the intracellular mechanisms of the magnitude-dependent actions of mechanical signals.

Methods: Chondrocytes isolated from rabbit articular cartilage were grown on flexible membranes.

Cleavage of CD14 and LBP by a protease from Prevotella intermedia.

Periodontitis is an inflammatory disease caused by subgingival microorganisms and their components, such as lipopolysaccharide (LPS). Responses of the host to LPS are mediated by CD14 and LPS-binding protein (LBP). In this study, it was determined that proteases from a periodontal pathogen, Prevotella intermedia, cleave CD14 and LBP, and thereby modulate the virulence of LPS.

Signal transduction by mechanical strain in chondrocytes.

Purpose Of Review: Exercise and passive motion exert reparative effects on inflamed joints, whereas excessive mechanical forces initiate cartilage destruction as observed in osteoarthritis. However, the intracellular mechanisms that convert mechanical signals into biochemical events responsible for cartilage destruction and repair remain paradoxical. This review summarizes how signals generated by mechanical stress may initiate repair or destruction of cartilage.

A central role for the nuclear factor-kappaB pathway in anti-inflammatory and proinflammatory actions of mechanical strain.

Mechanical signals play an integral role in bone homeostasis. These signals are observed at the interface of bone and teeth, where osteoblast-like periodontal ligament (PDL) cells constantly take part in bone formation and resorption in response to applied mechanical forces. Earlier, we reported that signals generated by tensile strain of low magnitude (TENS-L) are antiinflammatory, whereas tensile strain of high magnitude (TENS-H) is proinflammatory and catabolic.

Vascularization and tissue infiltration of a biodegradable polyurethane matrix.

Urethanes are frequently used in biomedical applications because of their excellent biocompatibility. However, their use has been limited to bioresistant polyurethanes. The aim of this study was to develop a nontoxic biodegradable polyurethane and to test its potential for tissue compatibility.

Aquaporin expression in developing human teeth and selected orofacial tissues.

The aquaporin (AQP) family of membrane channel proteins function as selective pores through which water, glycerol, and other small solutes cross the cell plasma membrane. To date, 11 members of this transporter family, designated AQP0-10, have been cloned and characterized in humans. The AQPs are differentially expressed in temporospatial patterns, where different AQPs demonstrate distinct tissue distributions that may reflect differing cell membrane transport functions.

Signaling by mechanical strain involves transcriptional regulation of proinflammatory genes in human periodontal ligament cells in vitro.

Intracellular signals generated by mechanical strain profoundly affect the metabolic function of osteoblast-like periodontal ligament (PDL) cells, which reside between the tooth and alveolar bone. In response to applied mechanical forces, PDL cells synthesize bone-resorptive cytokines to induce bone resorption at sites exposed to compressive forces and deposit bone at sites exposed to tensile forces in an environment primed for catabolic processes. The intracellular mechanisms that regulate this bone remodeling remain unclear.

Tuned aperture computed tomography to evaluate osseous healing.

Quantification of osseous healing is a challenging task, requiring expensive advanced imaging modalities. To improve diagnostic osseous imaging, we undertook this prospective study to explore the potential of Tuned Aperture Computed Tomography. Eighty defects in 20 rabbit mandibles, randomly carrying an osteoblast suspension or a polymer matrix or a combination thereof or no treatment, were imaged at 3, 6, 9, and 12 weeks post-surgery.

Fractal analyses of osseous healing using tuned aperture computed tomography images.

The aim of this study was to evaluate osseous healing in mandibular defects using fractal analyses on conventional radiographs and tuned aperture computed tomography (TACT; OrthoTACT, Instrumentarium Imaging, Helsinki, Finland) images. Eighty test sites on the inferior margins of rabbit mandibles were subject to lesion induction and treated with one of the following: no treatment (controls); osteoblasts only; polymer matrix only; or osteoblast-polymer matrix (OPM) combination. Images were acquired using conventional radiography and TACT, including unprocessed TACT (TACT-U) and iteratively restored TACT (TACT-IR).

Low magnitude of tensile strain inhibits IL-1beta-dependent induction of pro-inflammatory cytokines and induces synthesis of IL-10 in human periodontal ligament cells in vitro.

Applied mechanical loading induces inflammation in the periodontal ligament (PDL). However, the mechanisms involved in bone deposition at tension sites in an inflammatory environment are not clear. Here, in an in vitro model system, we show that equibiaxial tensile strain of low magnitude (TENS) provokes potent anti-inflammatory signals in PDL cells.

Cyclic tensile strain suppresses catabolic effects of interleukin-1beta in fibrochondrocytes from the temporomandibular joint.

Objective: To discern the effects of continuous passive motion on inflamed temporomandibular joints (TMJ).

Methods: The effects of continuous passive motion on TMJ were simulated by exposing primary cultures of rabbit TMJ fibrochondrocyte monolayers to cyclic tensile strain (CTS) in the presence of recombinant human interleukin-1beta (rHuIL-1beta) in vitro. The messenger RNA (mRNA) induction of rHuIL-1beta response elements was examined by semiquantitative reverse transcriptase-polymerase chain reaction.

[Cytokine-induced nitric oxide production of joint cartilage cells in continuous passive movement. Anti-inflammatory effect of continuous passive movement on chondrocytes: in vitro study].

Purpose: The temporomandibular joint is a place of motion where release of proinflammatory cytokines like interleukin-1 beta (IL-1 beta) induces cartilage destruction via production of nitric oxide (NO). The purpose of this study was to evaluate the effects of continuous passive motion in the form of cyclic stretch on the synthesis of inducible nitric oxide synthase (iNOS).

Methods: Articular chondrocytes were harvested from rabbit cartilage slices and cultured in F12 medium supplemented with 10% fetal calf serum.

A new peptide-based urethane polymer: synthesis, biodegradation, and potential to support cell growth in vitro.

A novel non-toxic biodegradable lysine-di-isocyanate (LDI)-based urethane polymer was developed for use in tissue engineering applications. This matrix was synthesized with highly purified LDI made from the lysine diethylester. The ethyl ester of LDI was polymerized with glycerol to form a prepolymer.

Cyclic tensile stress exerts antiinflammatory actions on chondrocytes by inhibiting inducible nitric oxide synthase.

Continuous passive motion manifests therapeutic effects on inflamed articular joints by an as-yet-unknown mechanism. Here, we show that application of cyclic tensile stress (CTS) in vitro abrogates the catabolic effects of IL-1beta on chondrocytes. The effects of CTS are mediated by down-regulation of IL-1beta-dependent inducible NO production, and are directly attributed to the inhibition of inducible NO synthase (iNOS) mRNA expression and protein synthesis.

Autoregulation of periodontal ligament cell phenotype and functions by transforming growth factor-beta1.

During orthodontic tooth movement, mechanical forces acting on periodontal ligament (PDL) cells induce the synthesis of mediators which alter the growth, differentiation, and secretory functions of cells of the PDL. Since the cells of the PDL represent a heterogeneous population, we examined mechanically stress-induced cytokine profiles in three separate clones of human osteoblast-like PDL cells. Of the four pro-inflammatory cytokines investigated, only IL-6 and TGF-beta1 were up-regulated in response to mechanical stress.

Regulation of periodontal ligament cell functions by interleukin-1beta.

Periodontal ligament (PDL) cells maintain the attachment of the tooth to alveolar bone. These cells reside at a site in which they are challenged frequently by bacterial products and proinflammatory cytokines, such as interleukin-1beta (IL-1beta), during infections. In our initial studies we observed that IL-1beta down-regulates the osteoblast-like characteristics of PDL cells in vitro.

Effects of sanguinarium, chlorhexidine and tetracycline on neutrophil viability and functions in vitro.

The effectiveness of an ideal antimicrobial agent depends on its ability to kill microbes with minimal toxicity to host cells. Depending on the treatment regimen, antimicrobial agents come into contact with host cells for various intervals of time. Sanguinarium (SANG), chlorhexidine (CHX) and tetracycline (TET) are 3 antimicrobial agents frequently used in the management of periodontal infections.

Altered Neutrophil Function in Localized Juvenile Periodontitis: Intrinsic or Induced?

Localized juvenile periodontitis (LJP) is an aggressive periodontal disease of familial nature. Neutrophils from a majority of patients with this disease exhibit decreased Chemotaxis with increased adherence, oxidative burst, and degranulation in response to opsonized bacteria. It is proposed that the biological basis for these altered neutrophil functions in LJP may be due either to intrinsic cell abnormalities or to the effect of factors present in the sera of LJP patients, which can modulate neutrophil functions.

Synthesis of proinflammatory cytokines by human gingival fibroblasts in response to lipopolysaccharides and interleukin-1 beta.

We have examined the ability of gingival fibroblasts (GF) to participate in inflammatory response and function as accessory immune cells. The accessory immune function of GF cells was evaluated by their ability to elaborate proinflammatory cytokines following stimulation with lipopolysaccharides and interleukin-1 beta (IL-1 beta). Using three separate clonally derived and characterized human gingival fibroblast (GF) cell lines, we demonstrate that LPS from Actinobacillus actinomycetemcomitans (Aa) and Escherichia coli (Ec) induce mRNA and synthesis of proinflammatory cytokines, IL-1 beta, IL-6 and IL-8.