The Contribution of Perilacunar Composition and Mechanical Properties to Whole-Bone Mechanical Outcomes in Streptozotocin-Induced Diabetes
AbstractOsteocytes are the most abundant cell type in bone and remodel their local perilacunar matrix in response to a variety of stimuli and diseases. How the perilacunar composition and mechanical properties are affected by type 1 diabetes (T1D), and the contribution of these local changes to the decline in whole-bone functional properties that occurs with diabetes remains unclear. 12 –14 week old C57/BL6 male mice were administered a series of low-dose streptozotocin injections and sacrificed at baseline (BL), 3 (D3) and 7 weeks (D7) following confirmation of diabetes, along with age-matched controls (C3, C7). Femor...
Source: Calcified Tissue International - June 1, 2023 Category: Orthopaedics Source Type: research
Examining Mechanisms for Voltage-Sensitive Calcium Channel-Mediated Secretion Events in Bone Cells
AbstractIn addition to their well-described functions in cell excitability, voltage-sensitive calcium channels (VSCCs) serve a critical role in calcium (Ca2+)-mediated secretion of pleiotropic paracrine and endocrine factors, including those produced in bone. Influx of Ca2+ through VSCCs activates intracellular signaling pathways to modulate a variety of cellular processes that include cell proliferation, differentiation, and bone adaptation in response to mechanical stimuli. Less well understood is the role of VSCCs in the control of bone and calcium homeostasis mediated through secreted factors. In this review, we discus...
Source: Calcified Tissue International - June 1, 2023 Category: Orthopaedics Source Type: research
The Contribution of Perilacunar Composition and Mechanical Properties to Whole-Bone Mechanical Outcomes in Streptozotocin-Induced Diabetes
AbstractOsteocytes are the most abundant cell type in bone and remodel their local perilacunar matrix in response to a variety of stimuli and diseases. How the perilacunar composition and mechanical properties are affected by type 1 diabetes (T1D), and the contribution of these local changes to the decline in whole-bone functional properties that occurs with diabetes remains unclear. 12 –14 week old C57/BL6 male mice were administered a series of low-dose streptozotocin injections and sacrificed at baseline (BL), 3 (D3) and 7 weeks (D7) following confirmation of diabetes, along with age-matched controls (C3, C7). Femor...
Source: Calcified Tissue International - June 1, 2023 Category: Orthopaedics Source Type: research
“Bone-SASP” in Skeletal Aging
AbstractSenescence is a complex cell state characterized by stable cell cycle arrest and a unique secretory pattern known as the senescence-associated secretory phenotype (SASP). The SASP factors, which are heterogeneous and tissue specific, normally include chemokines, cytokines, growth factors, adhesion molecules, and lipid components that can lead to multiple age-associated disorders by eliciting local and systemic consequences. The skeleton is a highly dynamic organ that changes constantly in shape and composition. Senescent cells in bone and bone marrow produce diverse SASP factors that induce alterations of the skele...
Source: Calcified Tissue International - May 31, 2023 Category: Orthopaedics Source Type: research
Bone and the Unfolded Protein Response: In Sickness and in Health
AbstractDifferentiation and optimal function of osteoblasts and osteoclasts are contingent on synthesis and maintenance of a healthy proteome. Impaired and/or altered secretory capacity of these skeletal cells is a primary driver of most skeletal diseases. The endoplasmic reticulum (ER) orchestrates the folding and maturation of membrane as well as secreted proteins at high rates within a calcium rich and oxidative organellar niche. Three ER membrane proteins monitor fidelity of protein processing in the ER and initiate an intricate signaling cascade known as the Unfolded Protein Response (UPR) to remediate accumulation of...
Source: Calcified Tissue International - May 27, 2023 Category: Orthopaedics Source Type: research
Megakaryocyte Secreted Factors Regulate Bone Marrow Niche Cells During Skeletal Homeostasis, Aging, and Disease
AbstractThe bone marrow microenvironment contains a diverse array of cell types under extensive regulatory control and provides for a novel and complex mechanism for bone regulation. Megakaryocytes (MKs) are one such cell type that potentially acts as a master regulator of the bone marrow microenvironment due to its effects on hematopoiesis, osteoblastogenesis, and osteoclastogenesis. While several of these processes are induced/inhibited through MK secreted factors, others are primarily regulated by direct cell –cell contact. Notably, the regulatory effects that MKs exert on these different cell populations has been fou...
Source: Calcified Tissue International - May 27, 2023 Category: Orthopaedics Source Type: research
Bone and the Unfolded Protein Response: In Sickness and in Health
AbstractDifferentiation and optimal function of osteoblasts and osteoclasts are contingent on synthesis and maintenance of a healthy proteome. Impaired and/or altered secretory capacity of these skeletal cells is a primary driver of most skeletal diseases. The endoplasmic reticulum (ER) orchestrates the folding and maturation of membrane as well as secreted proteins at high rates within a calcium rich and oxidative organellar niche. Three ER membrane proteins monitor fidelity of protein processing in the ER and initiate an intricate signaling cascade known as the Unfolded Protein Response (UPR) to remediate accumulation of...
Source: Calcified Tissue International - May 27, 2023 Category: Orthopaedics Source Type: research
Megakaryocyte Secreted Factors Regulate Bone Marrow Niche Cells During Skeletal Homeostasis, Aging, and Disease
AbstractThe bone marrow microenvironment contains a diverse array of cell types under extensive regulatory control and provides for a novel and complex mechanism for bone regulation. Megakaryocytes (MKs) are one such cell type that potentially acts as a master regulator of the bone marrow microenvironment due to its effects on hematopoiesis, osteoblastogenesis, and osteoclastogenesis. While several of these processes are induced/inhibited through MK secreted factors, others are primarily regulated by direct cell –cell contact. Notably, the regulatory effects that MKs exert on these different cell populations has been fou...
Source: Calcified Tissue International - May 27, 2023 Category: Orthopaedics Source Type: research
Alcohol Consumption and Measures of Sarcopenic Muscle Risk: Cross-Sectional and Prospective Associations Within the UK Biobank Study
AbstractAlcohol intake is a major modifiable risk factor for many diseases. Alcohol can also damage skeletal muscle health during ageing which in turn increases risk of sarcopenia, frailty and falls but this relationship is understudied. The aim of this study was to model the relationship between a full range of alcohol consumption and components of sarcopenic risk, skeletal muscle mass and function, in middle-aged and younger older-aged men and women. A cross-sectional analyses was undertaken of 196,561 white participants from the UK Biobank with longitudinal analysis also in 12,298 of these participants, with outcome mea...
Source: Calcified Tissue International - May 25, 2023 Category: Orthopaedics Source Type: research
Bone Mineral Density in Neurofibromatosis Type 1: A Systematic Review and Meta-Analysis
AbstractTo assess BMD in patients with neurofibromatosis type 1 (NF1) using systematic review and meta-analysis technique. Potentially eligible studies were identified from Medline and EMBASE databases from inception to February 2023 using search strategy that comprised terms for “Bone mineral density” and Neurofibromatosis type 1″. Eligible study must include adult or pediatric patients with NF1. The study must report mean Z-score with variance of total body, lumbar spine, femoral neck or total hip BMD of the studied patients. Point estimates with standard errors were retrieved from each study and were combined usin...
Source: Calcified Tissue International - May 23, 2023 Category: Orthopaedics Source Type: research
Metabolic Health and Disease: A Role of Osteokines?
AbstractMaintenance of skeletal health is tightly regulated by osteocytes, osteoblasts, and osteoclasts via coordinated secretion of bone-derived factors, termed osteokines. Disruption of this coordinated process due to aging and metabolic disease promotes loss of bone mass and increased risk of fracture. Indeed, growing evidence demonstrates that metabolic diseases, including type 2 diabetes, liver disease and cancer are accompanied by bone loss and altered osteokine levels. With the persistent prevalence of cancer and the growing epidemic of metabolic disorders, investigations into the role of inter-tissue communication ...
Source: Calcified Tissue International - May 17, 2023 Category: Orthopaedics Source Type: research
