Osteocyte Wnt/β-catenin pathway activation upon mechanical loading is altered in ovariectomized mice.

Estrogen levels decline in both sexes with age, but more dramatically in females. Activation of the Wnt/β-catenin signaling pathway is central to the regulation of bone mass accrual and maintenance and in response to mechanical loading. Using the ovariectomized mouse model we examined the effect of estrogen loss on the osteocyte's ability to activate the Wnt/β-catenin pathway following mechanical loading.

Estrogen Signaling in Bone.

Estrogen plays important roles in bone homeostasis throughout a person's life, including longitudinal bone growth, bone healing, and adaptation to mechanical forces. Estrogen exerts its action by binding to its multiple receptors in the cell membrane and cytoplasm. Until now at least three estrogen receptors (ER) have been reported: ER alpha (ERα), ER beta (ERβ), and G-protein coupled estrogen receptor 1 (GPER1) also known as GP30.

Age and gender related differences in load-strain response in C57Bl/6 mice.

We examined the changes in mechanical strain response of male and female mouse tibia and ulna, using axial compression tests, to assess age-related changes in tibiae and ulnae by a non-contact strain measurement technique called the digital image correlation (DIC) and the standard strain gage. A unique aspect of the study was to compare bones from the same animal to study variations in behavior with aging. This study was conducted using male and female C57Bl/6 mice at 6, 12 and 22 months of age (N=6-7 per age and sex) using three load levels.

Bone-Muscle Mutual Interactions.

Purpose Of Review: The purpose of this review is to describe the current state of our thinking regarding bone-muscle interactions beyond the mechanical perspective.

Recent Findings: Recent and prior evidence has begun to dissect many of the molecular mechanisms that bone and muscle use to communicate with each other and to modify each other's function. Several signaling factors produced by muscle and bone have emerged as potential mediators of these biochemical/molecular interactions.

Age-related and sex-specific effects on architectural properties and biomechanical response of the C57BL/6N mouse femur, tibia and ulna.

Aging is known to reduce bone quality and bone strength. We sought to determine how aging affects the biomechanical and architectural properties of various long bones, and if sex influences age related differences/changes. While researchers have extensively studied these changes in individual bones of mice, there is no comprehensive study of the changes in the bones from the same mice to study the changes with aging.

Multiscale finite element modeling of mechanical strains and fluid flow in osteocyte lacunocanalicular system.

Osteocytes form over 90% of the bone cells and are postulated to be mechanosensors responsible for regulating the function of osteoclasts and osteoblasts in bone modeling and remodeling. Physical activity results in mechanical loading on the bones. Osteocytes are thought to be the main mechanosensory cells in bone.

Determination of Elastic Modulus in Mouse Bones Using a Nondestructive Micro-Indentation Technique Using Reference Point Indentation.

The determination of the elastic modulus of bone is important in studying the response of bone to loading and is determined using a destructive three-point bending method. Reference point indentation (RPI), with one cycle of indentation, offers a nondestructive alternative to determine the elastic modulus. While the elastic modulus could be determined using a nondestructive procedure for ex vivo experiments, for in vivo testing, the three-point bending technique may not be practical and hence RPI is viewed as a potential alternative and explored in this study.

Muscle-Bone Crosstalk: Emerging Opportunities for Novel Therapeutic Approaches to Treat Musculoskeletal Pathologies.

Osteoporosis and sarcopenia are age-related musculoskeletal pathologies that often develop in parallel. Osteoporosis is characterized by a reduced bone mass and an increased fracture risk. Sarcopenia describes muscle wasting with an increasing risk of injuries due to falls.

Larger therapeutic window for steroid versus VEGF-A inhibitor in inflammatory angiogenesis: surprisingly similar impact on leukocyte infiltration.

Purpose: The current treatments against inflammatory angiogenesis are steroids and anti-VEGF-A, such as dexamethasone and bevacizumab, respectively. However, the therapeutic windows for dexamethasone and bevacizumab against inflammatory angiogenesis are unknown.

Methods: To investigate the therapeutic windows for dexamethasone and bevacizumab, we used the corneal pocket assay.

Activation of β-catenin signaling in MLO-Y4 osteocytic cells versus 2T3 osteoblastic cells by fluid flow shear stress and PGE2: Implications for the study of mechanosensation in bone.

The osteocyte is hypothesized to be the mechanosensory cell in bone. However, osteoblastic cell models have been most commonly used to investigate mechanisms of mechanosensation in bone. Therefore, we sought to determine if differences might exist between osteocytic and osteoblastic cell models relative to the activation of β-catenin signaling in MLO-Y4 osteocytic, 2T3 osteoblastic and primary neonatal calvarial cells (NCCs) in response to pulsatile fluid flow shear stress (PFFSS).

Blood vessel endothelial VEGFR-2 delays lymphangiogenesis: an endogenous trapping mechanism links lymph- and angiogenesis.

Angio- and lymphangiogenesis are inherently related processes. However, how blood and lymphatic vessels regulate each other is unknown. This work introduces a novel mechanism explaining the temporal and spatial relation of blood and lymphatic vessels.

Atrial natriuretic peptide reduces vascular leakage and choroidal neovascularization.

Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however, its role in vascular leakage and angiogenesis is unknown. In vitro, retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to 1 micromol/L), and/or isatin, an ANP receptor antagonist.