An LGR4 agonist activates the GSK‑3β pathway to inhibit RANK‑RANKL signaling during osteoclastogenesis in bone marrow‑derived macrophages.

The binding between receptor‑activated nuclear factor‑κB (RANK) and the RANK ligand (RANKL) during osteoclast development is an important target for drugs that treat osteoporosis. The leucine‑rich repeat‑containing G‑protein‑coupled receptor 4 (LGR4) acts as a negative regulator of RANK‑RANKL that suppresses canonical RANK signaling during osteoclast differentiation. Therefore, LGR4 agonists may be useful in inhibiting osteoclastogenesis and effectively treating osteoporosis.

Effect of HDAC9 inhibition on epithelial-mesenchymal transition in CD133+ prostate cancer cell lines.

A small fraction of cancer cells known as cancer stem cells (CSCs) are considered to give rise to differentiated cancer cells and have been proposed to predict cancer recurrence and metastasis. There is further evidence that CSCs may act as metastatic precursors of epithelial-mesenchymal transition (EMT). In the present study, we investigated the key molecules involved in maintaining the stability of CSCs by inducing ectopic overexpression of CD133 to characterize EMT in human prostate cancer cell lines, including PC-3, DU145, and LnCaP cells.

A novel modified RANKL variant can prevent osteoporosis by acting as a vaccine and an inhibitor.

Background: The discovery of receptor activator of nuclear factor-ĸB ligand (RANKL) as the final effector in the pathogenesis of osteoporosis has led to a better understanding of bone remodeling. When RANKL binds to its receptor (RANK), osteoclastic differentiation and activation are initiated. Herein, we propose a strategy using a novel RANKL variant as a competitive inhibitor for RANKL.

Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL.

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK-RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.

Effect of CD133 overexpression on bone metastasis in prostate cancer cell line LNCaP.

Prostate cancer (PC) metastasizes to the bone, and a small number of cancer cells, described as cancer stem cells (CSCs), have the ability to differentiate into tumor cells. CSCs are responsible for tumor recurrence and metastases. In the present study, we examined whether ectopic overexpression of CD133, a key molecule maintaining the stability of CSCs in the human PC cell line, LnCaP, caused bone metastasis in a mouse model.

Regulation of Osteosclerosis by Inoculated Cd133 PC3 Cells in Bone-marrow Microenvironmental Niches.

Bone is the most common site of prostate cancer (PC) metastasis. Studies suggest that cancer stem cells (CSCs) are associated with stemness characteristics, providing some support for the concept that CSCs act as osteosclerotic precursors in bone microenvironmental niches. Here, we asked whether ectopic overexpression of CD133 maintains stability of CSCs in human PC cell lines and induces the changes of molecular features in the bone microenvironment.

Real-time imaging of metastatic bone tumors with a targeted near-infrared fluorophore.

Tumors of the prostate or breast are particularly likely to metastasize to the bone, and early diagnosis of metastatic bone tumors is important for designing an effective treatment strategy. Imaging modalities for the detection of bone metastasis are limited, and radiation-based techniques are commonly used. Here, we investigated the efficacy of selective near-infrared (NIR) fluorescence detection of metastatic bone tumors and its role in the detection of bone metastasis in prostate and breast cancer cell lines and in a xenograft mouse model.

Ectopic overexpression of CD133 in HNSCC makes it resistant to commonly used chemotherapeutics.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world. Resistance to cytotoxic chemotherapy is a major cause of mortality in patients with HNSCC. A small subset of cancer cells called cancer stem cells (CSCs) may be key contributors to drug resistance and tumor recurrence in HNSCC.

Comparison of the alendronate and irradiation with a light-emitting diode (LED) on murine osteoclastogenesis.

Photomodulation therapy (PBMT) using light-emitting diode (LED) has been proposed as an alternative to conventional osteoporosis therapies. Our aim was to determine the effect of irradiation with a light-emitting diode on receptor activator of NF-κB ligand (RANKL)-mediated differentiation of mouse bone marrow macrophages into osteoclasts and compare it to alendronate treatment. The cells were irradiated with LED at 635±10 nm, 9-cm spot size, 5 mW/cm, and 18 J for 60 min/day in a CO incubator.

Regulation of RANKL-Induced Osteoclastogenesis by 635-nm Light-Emitting Diode Irradiation Via HSP27 in Bone Marrow-Derived Macrophages.

Objective: This study was designed to investigate the effect of 635-nm irradiation from a light-emitting diode (LED) on osteoclastogenesis in receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-stimulated mouse bone marrow-derived macrophages (BMMs). We determined whether 635-nm irradiation modulated the RANKL-induced osteoclastic signaling pathway in heat shock protein-27 (HSP27)-silenced cells and analyzed the functional cross talk between these factors in osteoclastic differentiation and activation.

Background: HSP27, a member of the small HSP family, regulates oxidative stress.

Effect of CD133 overexpression on the epithelial-to-mesenchymal transition in oral cancer cell lines.

Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world. In OSCC, CD133 promotes tumor invasion and metastasis by inducing the epithelial-to-mesenchymal transition (EMT). A small subset of cancer cells known as cancer stem cells (CSCs) are thought to give rise to differentiated tumor cells and to predict tumor recurrence and metastases, i.

Effects of light-emitting diode irradiation on RANKL-induced osteoclastogenesis.

Background And Objective: Bone homeostasis is maintained by a balance between osteoblastic bone formation and osteoclastic bone resorption, where intracellular reactive oxygen species (ROS) are crucial mediators of osteoclastogenesis. Recently, low-level light therapy (LLLT), a form of laser medicine used in various clinical fields, was shown to alleviate oxidative stress by scavenging intracellular ROS. The present study aimed to investigate the impact of 635 nm irradiation from a light-emitting diode (LED) on osteoclastogenesis from receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-stimulated mouse bone marrow-derived macrophages (BMMs).

Biological Effects of the Herbal Plant-Derived Phytoestrogen Bavachin in Primary Rat Chondrocytes.

The aim of this study was to examine the anabolic and anticatabolic functions of bavachin in primary rat chondrocytes. With bavachin treatment, chondrocytes survived for 21 d without cell proliferation, and the proteoglycan content and extracellular matrix increased. Short-term monolayer culture of chondrocytes showed that gene induction of both aggrecan and collagen type II, major extracellular matrix components, was significantly upregulated by bavachin.

Development of an Experimental Animal Model for Lower Back Pain by Percutaneous Injury-Induced Lumbar Facet Joint Osteoarthritis.

We report generation and characterization of pain-related behavior in a minimally invasive facet joint degeneration (FJD) animal model in rats. FJD was produced by a non-open percutaneous puncture-induced injury on the right lumbar FJs at three consecutive levels. Pressure hyperalgesia in the lower back was assessed by measuring the vocalization response to pressure from a force transducer.

Anti-inflammatory effect of 635 nm irradiations on in vitro direct/indirect irradiation model.

Low-level laser therapy (LLLT) has been promoted for its beneficial effects on tissue healing and pain relief. As during laser treatment it is possible to irradiate only a small area of the surface body or wound and, correspondingly, of a very small volume of the circulating blood, it is necessary to explain how its photomodification can lead to a wide spectrum of therapeutic effects. To establish the experimental model for indirect irradiation, irradiation with 635 nm was performed on immortalized human gingival fibroblasts (IGFs) in the presence of Porphyromonas gingivalis lipopolysaccharides (LPS).

Radiologic evaluation of degeneration in isthmic and degenerative spondylolisthesis.

Study Design: A cross-sectional imaging study.

Purpose: The objective was to assess the degree of degeneration and the associated factors through imaging studies of the lesion segment and the adjacent superior and inferior segments of isthmic and degenerative spondylolisthesis.

Overview Of Literature: Few articles existed for degeneration and related factors in isthmic and degenerative spondylolisthesis.

Magnesium in a polyethylene glycol formulation provides neuroprotection after unilateral cervical spinal cord injury.

Study Design: Experimental animal study.

Objective: To investigate the neuroprotective efficacy of this magnesium in polyethylene glycol (PEG) formulation in a contusive model of cervical spinal cord injury (SCI).

Summary Of Background Data: Intravenously administered magnesium has been extensively investigated as a neuroprotective agent in animal models of SCI, stroke, and traumatic brain injuries, and has been evaluated in large scale clinical trials for the latter 2 indications.

Life-threatening posterior circumflex humeral artery injury secondary to fracture-dislocation of the proximal humerus.

Proximal humeral fractures account for 4% to 5% of all fractures, and most of these are minimally displaced and less prone to neurovascular injuries. This article presents a case of a 65-year-old man who injured the posterior circumflex humeral artery following a fracture dislocation of the proximal humerus leading to a life-threatening hemorrhagic complication during surgical fixation of the dislocated proximal humeral fracture. Preoperative vital signs were normal.

Carbachol regulates pacemaker activities in cultured interstitial cells of Cajal from the mouse small intestine.

We studied the effect of carbachol on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine by muscarinic stimulation using a whole cell patch clamp technique and Ca2+-imaging. ICC generated periodic pacemaker potentials in the current-clamp mode and generated spontaneous inward pacemaker currents at a holding potential of-70 mV. Exposure to carbachol depolarized the membrane and produced tonic inward pacemaker currents with a decrease in the frequency and amplitude of the pacemaker currents.

Ape1/Ref-1 induces glial cell-derived neurotropic factor (GDNF) responsiveness by upregulating GDNF receptor alpha1 expression.

Apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) dysregulation has been identified in several human tumors and in patients with a variety of neurodegenerative diseases. However, the function of Ape1/Ref-1 is unclear. We show here that Ape1/Ref-1 increases the expression of glial cell-derived neurotropic factor (GDNF) receptor alpha1 (GFRalpha1), a key receptor for GDNF.

Protein phosphatase 5 regulates the function of 53BP1 after neocarzinostatin-induced DNA damage.

53BP1 (p53-binding protein 1) is a conserved nuclear protein that is phosphorylated in response to DNA damage and rapidly recruited to the site of DNA double strand breaks, demonstrating its role in the early events to DNA damage and repair of damaged DNA. In this study, we used the yeast two-hybrid system to identify proteins that interact with 53BP1. Identification and characterization of 53BP1 protein interactions may help to further elucidate the function and regulation of 53BP1.

Hypothermia for spinal cord injury.

Background Context: Interest in systemic and local hypothermia extends back over many decades, and both have been investigated as potential neuroprotective interventions in a number of clinical settings, including traumatic brain injury, stroke, cardiac arrest, and both intracranial and thoracoabdominal aortic aneurysm surgery. The recent use of systemic hypothermia in an injured National Football League football player has focused a great deal of attention on the potential use of hypothermia in acute spinal cord injury.

Purpose: To provide spinal clinicians with an overview of the biological rationale for using hypothermia, the past studies and current clinical applications of hypothermia, and the basic science studies and clinical reports of the use of hypothermia in acute traumatic spinal cord injury.

Delayed treatment of spinal cord injury with erythropoietin or darbepoetin--a lack of neuroprotective efficacy in a contusion model of cord injury.

A number of drugs commonly used for a variety of clinical indications have been found recently to have substantial neuroprotective properties, raising the potential for rapid translation into human clinical trials of spinal cord injury (SCI). In this study we compared the neuroprotective efficacy of erythropoietin and a derivative of it, darbepoetin, in an acute model of thoracic SCI. Sprague-Dawley rats were randomized to receive erythropoietin (5000 IU/kg), darbepoetin (10 mug/kg), or saline, as a single intravenous injection 1 h after a thoracic contusion SCI.

KIOM-79 inhibits LPS-induced iNOS gene expression by blocking NF-kappaB/Rel and p38 kinase activation in murine macrophages.

We demonstrate that KIOM-79, combined extracts obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of RAW 264.

The relationship between disc degeneration and morphologic changes in the intervertebral foramen of the cervical spine: a cadaveric MRI and CT study.

A cadaveric study was performed to investigate the relationship between disc degeneration and morphological changes in the intervertebral foramen of cervical spine, including the effect on the nerve root. Seven fresh frozen human cadavers were dissected from C1 to T1, preserving the ligaments, capsules, intervertebral disc and the neural structures. The specimens were scanned with MRI and then scanned through CT scan in the upright position.