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.

Comparison of Helical Blade Systems for Osteoporotic Intertrochanteric Fractures Using Biomechanical Analysis and Clinical Assessments.

: This study aimed to compare the biomechanical properties and outcomes of osteoporotic intertrochanteric fractures treated with two different helical blade systems, the trochanteric fixation nail-advanced (TFNA) and proximal femoral nail antirotation II (PFNA), to evaluate the efficacy and safety of the newly introduced TFNA system. : A biomechanical comparison of the two helical blades was performed using uniaxial compression tests on polyurethane foam blocks of different densities. The peak resistance (PR) and accumulated resistance (AR) were measured during the 20 mm advancement through the test block.

Impact of Capsulotomy on Hip Biomechanics during Arthroscopy.

: Anterior capsulotomy is routinely performed in hip arthroscopy to improve joint visualization; however, this can partly or completely disrupt the stabilizing ligaments of the hip. This study aimed to report the effects of conventional and extensive arthroscopic capsulotomies on hip stability. : Eight freshly frozen cadaveric pelvises were used in this study.

Molecular Tuning of IR-786 for Improved Tumor Imaging and Photothermal Therapy.

A tumor-targeted near-infrared (NIR) fluorophore CA800Cl was developed based on commercially available IR-786 by modulating its physicochemical properties. IR-786, a hydrophobic cationic heptamethine cyanine fluorophore, was previously recognized as a mitochondria-targeting NIR agent with excellent optical properties. Owing to the poor tumor specificity of IR-786 itself, in vivo studies on tumor-targeted imaging have not yet been investigated.

Osteoporosis therapies and their mechanisms of action (Review).

Osteoporosis is a common disease that affects millions of patients worldwide and is most common in menopausal women. The main characteristics of osteoporosis are low bone density and increased risk of fractures due to deterioration of the bone architecture. Osteoporosis is a chronic disease that is difficult to treat; thus, investigations into novel effective therapeutic methods are required.

Immunization With RANKL Inhibits Osteolytic Bone Metastasis in Breast Cancer.

Breast cancer cells often metastasize to bone. Accumulating evidence suggests that inhibiting the receptor activator of nuclear factor-κB ligand (RANKL) not only leads to reduced bone metastasis of breast cancer but also has antitumoral effects. Here, we used mutant receptor activator of nuclear factor-κB ligand (RANKLM) as a vaccine for active immunization to induce antibodies for immunotherapy of bone metastatic cancer.

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.

RANKL immunisation inhibits prostate cancer metastasis by modulating EMT through a RANKL-dependent pathway.

Prostate cancer (PCa) morbidity in the majority of patients is due to metastatic events, which are a clinical obstacle. Therefore, a better understanding of the mechanism underlying metastasis is imperative if we are to develop novel therapeutic strategies. Receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL) regulates bone remodelling.

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.

Role of / and During Irradiation in a PMA-Induced Inflammatory Model.

Sphingosine kinase 1 () and heat shock protein 27 () are important for antioxidant and anti-inflammatory effects after red light irradiation in an inflammatory model. The purpose of the present study was to evaluate whether and work independently or are dependent on some other regulator after 625 nm light-emitting diode irradiation in the human keratinocyte (HaCaT) cell line. Differentially expressed genes (DEGs) were identified between groups with or without 625 nm photobiomodulation (PBM) in the inflammatory model.

Zwitterionic near-infrared fluorophore for targeted photothermal cancer therapy.

Precise photothermal cancer therapy still relies on the development of multifunctional theranostic agents to integrate tumor-specific targeting, imaging, and therapy. In this study, we identified the zwitterionic near-infrared (NIR) fluorophore ZW800-Cl, an analog of the well-known ZW800-1, and found that it preferentially accumulated in tumors in various xenograft models. We have demonstrated that the optical and physicochemical properties of ZW800-Cl are similar to those of ZW800-1, but it has a unique tumor targetability.

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.

Transmembrane protein 64 modulates prostate tumor progression by regulating Wnt3a secretion.

Wnt3a is a glycosylated ligand that activates the β-catenin-dependent signaling pathway. Wnt signaling is also important in the prostate tumor microenvironment, and Wnt proteins secreted by the tumor stroma promote resistance to therapy. Bioactive Wnt3a production requires a number of dedicated factors in the secretory cell, but their coordinated functions are not fully understood.

Bioluminescence and near-infrared fluorescence imaging for detection of metastatic bone tumors.

Bioluminescence imaging is being increasingly utilized in biological research. However, since the most commonly used firefly luciferase generates relatively weak bioluminescent signals, detection of low numbers of luciferase-expressing cells in vivo is challenging. The weak signal makes it difficult to detect cells located in deep tissues, which is problematic for preclinical research in tumor metastasis.

Low-Dose Evans Blue Dye for Near-Infrared Fluorescence Imaging in Photothrombotic Stroke Model.

Evans blue dye (EBD) is the most common indicator to analyze the extent of blood-brain barrier (BBB) breakdown in several neurological disease models. However, the high-dose of EBD (51.9 mg/kg) is usually required for visualization of blue color by the human eye that brings potential safety issues.

Injectable visible light-cured glycol chitosan hydrogels with controlled release of anticancer drugs for local cancer therapy in vivo: a feasible study.

Currently available chemotherapy is associated with serious side effects, and therefore novel drug delivery systems (DDSs) are required to specifically deliver anticancer drugs to targeted sites. In this study, we evaluated the feasibility of visible light-cured glycol chitosan (GC) hydrogels with controlled release of doxorubicin⋅hydrochloride (DOX⋅HCl) as local DDSs for effective cancer therapy in vivo. The storage modulus of the hydrogel precursor solutions was increased as a function of visible light irradiation time.

Rapid Differential Diagnosis of Breast Microcalcification Using Targeted Near-Infrared Fluorophores.

Early detection and differential diagnosis of breast microcalcifications are of significant importance in effective treatment of early breast cancer, because mineral composition of breast calcification is directly associated with different pathological states. However, applying image-based modalities for component identification in breast calcification remains challenging, because no calcification-specific contrast agent is available to distinguish between benign and malignant (type I and type II, respectively) calcifications of breast lesions. In this study, real-time near-infrared (NIR) fluorescence imaging of breast microcalcifications using targeted NIR fluorophores in combination with dual-channel NIR fluorescence imaging system is reported.

ZW800-1 for Assessment of Blood-Brain Barrier Disruption in a Photothrombotic Stroke Model.

Since it is known that serum albumin-bound dyes can cross the blood-brain barrier (BBB) after ischemia, Evans Blue dye is commonly used to assess BBB disruption because of its rapid binding to serum albumin. In addition, indocyanine green (ICG), a clinically available dye, binds to serum proteins that could also be used for assessment of BBB impairment. Unlike these near-infrared (NIR) dyes, zwitterionic NIR fluorophore (ZW800-1) shows no serum binding, ultralow non-specific tissue uptake, and rapid elimination from the body via renal filtration.

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.

Chemoresistance to 5-FU inhibited by 635 nm LED irradiation in CD133+ KB cell line.

Consistent with cancer stem cell theory, a small fraction of cancer cells, described as cancer stem cells (CSCs), may promote tumor recurrence and anti-cancer drug resistance. Therefore, much effort has been devoted to the development of CSC targeted therapy to vanquish drug resistance. In this study, we have investigated the effect of multiple light-emitting diode (LED) irradiation treatments with conventional anti-cancer drugs on CSC-like oral cancer cells that acquired stemness by ectopic over expression of CD133.

Relationship of cytokine levels and clinical effect on platelet-rich plasma-treated lateral epicondylitis.

Lateral epicondylitis (LE) is difficult to manage and can result in significant patient morbidity. Currently, the clinical use of platelet-rich plasma (PRP) for painful tendons has received attention, but its efficacy remains controversial. This study aimed to investigate the clinical effects of PRP and its biological components.