Non-contact small animal fluorescence imaging system for simultaneous multi-directional angular-dependent data acquisition.

We present a novel non-contact small animal fluorescent molecular tomography (FMT) imaging system. At the heart of the system is a new mirror-based imaging head that was designed to provide 360-degree measurement data from an entire animal surface in one step. This imaging head consists of two conical mirrors, which considerably reduce multiple back reflections between the animal and mirror surfaces.

Effects of biomechanical forces on signaling in the cortical collecting duct (CCD).

An increase in tubular fluid flow rate (TFF) stimulates Na reabsorption and K secretion in the cortical collecting duct (CCD) and subjects cells therein to biomechanical forces including fluid shear stress (FSS) and circumferential stretch (CS). Intracellular MAPK and extracellular autocrine/paracrine PGE2 signaling regulate cation transport in the CCD and, at least in other systems, are affected by biomechanical forces. We hypothesized that FSS and CS differentially affect MAPK signaling and PGE2 release to modulate cation transport in the CCD.

Proteomic identification of 14-3-3ϵ as a linker protein between pERK1/2 inhibition and BIM upregulation in human osteosarcoma cells.

Despite advancements in multimodality chemotherapy, conventional cytotoxic treatments still remain ineffective for a subset of patients with aggressive metastatic or multifocal osteosarcoma. It has been shown that pERK1/2 inhibition enhances chemosensitivity to doxorubicin and promotes osteosarcoma cell death in vivo and in vitro. One of the pro-apoptotic mechanisms is upregulation of Bim by pERK1/2 inhibitors.

Nuclear presence of nuclear factor of activated T cells (NFAT) c3 and c4 is required for Toll-like receptor-activated innate inflammatory response of monocytes/macrophages.

Nuclear factor of activated T cells (NFATs) are crucial transcription factors that tightly control proinflammatory cytokine expression for adaptive immunity in T and B lymphocytes. However, little is known about the role of NFATs for innate immunity in macrophages. In this study, we report that NFAT is required for Toll-like receptor (TLR)-initiated innate immune responses in bone marrow-derived macrophages (BMMs).

Targeting inflammatory kinase as an adjuvant treatment for osteosarcomas.

Background: A subset of patients with aggressive osteosarcomas responds poorly to conventional cytotoxic chemotherapy. Recent evidence from studies involving the liver, skin, stomach, and colon suggests that carcinogenesis is associated with inflammation. Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) has diverse roles in cancer and inflammation.

Nuclear factor of activated T cells mediates fluid shear stress- and tensile strain-induced Cox2 in human and murine bone cells.

Mechanical loading such as interstitial fluid shear stress and tensile strain stimulates bone cells, which respond by changing bone mass and structure to maintain optimal skeletal architecture. Bone cells also adapt to bone implants and altered mechanical loading. Osseous integration between host bone and implants is a prerequisite for the stability of implants.

Enhancement of periprosthetic bone quality with topical hydroxyapatite-bisphosphonate composite.

Background: Implant loosening is associated with inflammatory bone loss induced by ultra-high molecular weight polyethylene wear debris. We hypothesized that a hydroxyapatite-bisphosphonate composite improves periprosthetic bone quality and osseous integration of an intramedullary implant even in the presence of ultra-high molecular weight polyethylene particles in an experimental rat femur model.

Methods: A preliminary in vitro study determined the optimal concentration of zoledronate (50 microM) that would maximally decrease osteoclasts without harming osteoblasts.

What are the local and systemic biologic reactions and mediators to wear debris, and what host factors determine or modulate the biologic response to wear particles?

New clinical and basic science data on the cellular and molecular mechanisms by which wear particles stimulate the host inflammatory response have provided deeper insight into the pathophysiology of periprosthetic bone loss. Interactions among wear particles, macrophages, osteoblasts, bone marrow-derived mesenchymal stem cells, fibroblasts, endothelial cells, and T cells contribute to the production of pro-inflammatory and pro-osteoclastogenic cytokines such as TNF-alpha, RANKL, M-SCF, PGE2, IL-1, IL-6, and IL-8. These cytokines not only promote osteoclastogenesis but interfere with osteogenesis led by osteoprogenitor cells.

Coronal and sagittal plane correction in adolescent idiopathic scoliosis: a comparison between all pedicle screw versus hybrid thoracic hook lumbar screw constructs.

Study Design: This was a retrospective cohort study using a previously matched convenience sample of 34 patients.

Objective: This study sought to determine the relative corrective benefits of these 2 types of constructs in the correction of coronal and sagittal curves in patients with adolescent idiopathic scoliosis (AIS). In addition, the 2 constructs were compared for coronal and sagittal balance.

Mechanical loading differentially regulates membrane-bound and soluble RANKL availability in MC3T3-E1 cells.

To understand the biochemical response of RANKL in response to mechanical loading, MC3T3-E1 cells were biequiaxially stretched. A murine RANKL cDNA with double epitopes, pEF6 HA-RANKL-V5His, was transfected into MC3T3-E1 cells, which were then stretched. Endogenous RANKL protein expression increased in response to mechanical loading.

Operative lengthening of the humerus: indications, benefits, and complications.

The purpose of this study was to determine the benefits and risks of humeral lengthening procedures. Distraction osteogenesis was performed in 19 humeri on 16 patients (9 males, 7 females). The mean age at the time of lengthening was 11.

Extranodal Rosai-Dorfman disease of bone, subcutaneous tissue and paranasal sinus mucosa with a review of its pathogenesis.

We report an unusual case of extranodal Rosai-Dorfman disease presenting in a 36-year-old man with lesions of bone, subcutaneous tissue of the arm and maxillary sinus mucosa unassociated with lymphadenopathy or systemic symptoms. These lesions appeared metachronously within a 6-month period. The diagnostic light microscopic and immunohistochemical findings and pathogenesis of this interesting disease are discussed.

mu-Calpain regulates receptor activator of NF-kappaB ligand (RANKL)-supported osteoclastogenesis via NF-kappaB activation in RAW 264.7 cells.

To clarify the role of calpain in the receptor activator of NF-kappaB ligand (RANKL)-supported osteoclastogenesis, RANKL-induced calpain activation was examined by using murine RAW 264.7 cells and bone marrow-derived monocyte/macrophage progenitors. We found that calpain activity increased in response to RANKL in both cell types based on alpha-spectrinolysis and that mu-calpain, rather than m-calpain, was activated during RANKL-supported osteoclastogenesis in RAW 264.

Zoledronate induces apoptosis in cells from fibro-cellular membrane of unicameral bone cyst (UBC).

Unicameral bone cyst (UBC) is a benign cystic lesion in children which is prone to fracture. Various treatments are available, but recurrence after different types of percutaneous injection therapy can cause bone destruction and pathologic fracture. The potential therapeutic effects of anti-resorptive agents, such as bisphosphonates, have not been investigated for UBC.

Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone.

Giant cell tumor (GCT) of bone is a unique bone lesion that is characterized by an excessive number of multinucleated osteoclasts. GCT consists of neoplastic stromal cells, multinucleated osteoclasts and their precursors, thus serving as a naturally occurring human disease model for the study of osteoclastogenesis. It still remains unclear how stromal cells of GCT recruit osteoclast precursors.

Diagnostic value and limitations of fluorine-18 fluorodeoxyglucose positron emission tomography for cartilaginous tumors of bone.

Background: A variety of imaging modalities are currently used for the preoperative evaluation of cartilage tumors. Although the anatomic details of the lesions are demonstrated well on computerized tomography and magnetic resonance images, those studies yield little information about the biologic activity of the tumors. In this study, we investigated the glucose metabolism of cartilage tumors measured by positron emission tomography and its correlation with histopathologic grades.

Bisphosphonates may reduce recurrence in giant cell tumor by inducing apoptosis.

Giant cell tumor of bone is an aggressive tumor characterized by extensive bone destruction and high recurrence rates. This tumor consists of stromal cells and hematopoietic cells that interact in an autocrine manner to produce tumoral osteoclastogenesis and bone resorption. This autocrine regulation may be disrupted by novel therapeutic agents.

Synovial chondromatosis of the foot.

Synovial chondromatosis rarely occurs in the foot. Five patients with synovial chondromatosis in the foot were treated with excision. There were four men and one woman with a mean age of 37 years (range, 19-58 years).

In situ pinning of hip for stable slipped capital femoral epiphysis on a radiolucent operating table.

Patients with stable slipped capital femoral epiphysis (SCFE) usually can ambulate at the time of diagnosis. Satisfactory results have been reported after percutaneous in situ pinning using a fracture table. The authors describe a technique to determine the skin-pin entry point for percutaneous pinning of the hip on a regular radiolucent operating table.

Repair of bone allograft fracture using bone morphogenetic protein-2.

Long-term clinical data have shown that reconstruction using bone allografts provide adequate function after extensive tumor surgery. Complications such as nonunion of allograft-host interface, infection, and allograft fracture often require major revision surgeries. Allograft fractures usually do not induce the same repair process that is seen in normal fracture healing.

Magnetic resonance imaging depiction of tight iliotibial band in melorheostosis associated with severe external rotation deformity, limb shortening and patellar dislocation in planning surgical correction.

We present the case of a 14-year-old male with melorhesotosis and severe iliotibial band tightness which was associated with femoral shortening, severe external rotational deformity of the femur, genu valgum and patellar dislocation in the right lower extremity. Skeletal survey revealed irregular radiodense streaks involving the pelvis, femoral head, femoral shaft, distal femoral epiphysis, talus and middle phalangeal bones of the foot. Magnetic resonance (MR) imaging showed thickening of the iliotibial band in addition to low MR signal changes in the bone.

Novel translocation (9;12)(q22;q24) in secondary chondrosarcoma arising from hereditary multiple exostosis.

We report a new translocation in a patient with a history of hereditary multiple exostosis (HME) who developed a recurrent grade I chondrosarcoma involving the sacrum and retroperitoneum. Karyotypic analysis of the tumor revealed a sole chromosome abnormality t(9;12)(q22;q24.3).