Integrin α2β1 deficiency enhances osteogenesis via BMP-2 signaling for accelerated fracture repair.

Previous studies have shown that the absence of the collagen-binding integrin α2β1 confers protection against osteoporosis, primarily by enhancing osteoblast-mediated matrix formation, with a particular increase in collagen type I production. This study aimed to elucidate the mechanism underlying this increased matrix production. Our findings demonstrate that osteoblasts lacking integrin α2 secrete a pro-osteogenic factor that activates both TGF-β and BMP signaling pathways.

The Role of Alumni Networks and Career Advising in Early Career Stability of Urologists: Results of a Multi-institutional Study.

Objective: To characterize training program and early career factors that impact decision-making and job retention following graduation in a diverse population of urologists.

Materials And Methods: We performed a computer-based survey distributed to residency graduates from 25 urology training programs. Five focus institutions were identified with a goal >30% response rate.

Wrap It! Preventive Antimicrobial Treatment Shows No Negative Effects on Tenocytes and Tendons-A Comprehensive Approach.

Unlabelled: Although the rate of infection after the reconstruction of a ruptured anterior cruciate ligament (ACL) is low, prophylactic incubation of the graft with vancomycin (Vanco-wrap or vancomycin soaking) is routinely performed. A cytotoxic effect of vancomycin is reported for several cell types, and the prophylactic treatment might prevent infection but harm the tissue and cells.

Aim: A comprehensive study was performed to investigate the effect of vancomycin on tendon tissue and isolated tenocytes using cell viability, molecular and mechanical analysis.

Transdermal carbon monoxide delivery.

Overuse injuries or acute trauma in joints often lead to painful tendinopathy, and pharmacological treatment effects are limited. The site of the disease is hard to reach with drugs, both systemically and through the skin. Therapeutic gases may close this gap, as they permeate easier through tissues than conventional small molecules.

Behavioral Voluntary and Social Bioassays Enabling Identification of Complex and Sex-Dependent Pain-(-Related) Phenotypes in Rats with Bone Cancer.

Cancer-induced bone pain (CIBP) is a common and devastating symptom with limited treatment options in patients, significantly affecting their quality of life. The use of rodent models is the most common approach to uncovering the mechanisms underlying CIBP; however, the translation of results to the clinic may be hindered because the assessment of pain-related behavior is often based exclusively on reflexive-based methods, which are only partially indicative of relevant pain in patients. To improve the accuracy and strength of the preclinical, experimental model of CIBP in rodents, we used a battery of multimodal behavioral tests that were also aimed at identifying rodent-specific behavioral components by using a home-cage monitoring assay (HCM).

[Modern imaging of the pulmonary hilum : Anatomy, pathologies, pitfalls].

Background: Modern medical imaging is a key component of efficient in- and out-patient precision medicine. Conventional radiography and computer tomography scans (CT) are among the most frequent radiologic exams. Medical imaging plays a key role in target-oriented medicine.

Influence of the Peripheral Nervous System on Murine Osteoporotic Fracture Healing and Fracture-Induced Hyperalgesia.

Osteoporotic fractures are often linked to persisting chronic pain and poor healing outcomes. Substance P (SP), α-calcitonin gene-related peptide (α-CGRP) and sympathetic neurotransmitters are involved in bone remodeling after trauma and nociceptive processes, e.g.

Performance of virtual non-contrast images generated on clinical photon-counting detector CT for emphysema quantification: proof of concept.

Objective: To evaluate the performance of virtual non-contrast images (VNC) compared to true non-contrast (TNC) images in photon-counting detector computed tomography (PCD-CT) for the evaluation of lung parenchyma and emphysema quantification.

Methods: 65 (mean age 73 years; 48 male) consecutive patients who underwent a three-phase (non-contrast, arterial and venous) chest/abdomen CT on a first-generation dual-source PCD-CT were retrospectively included. Scans were performed in the multienergy (QuantumPlus) mode at 120 kV with 70 ml intravenous contrast agent at an injection rate of 4 ml s.

Human Sex Matters: Y-Linked Lysine Demethylase 5D Drives Accelerated Male Craniofacial Osteogenic Differentiation.

Female sex is increasingly associated with a loss of bone mass during aging and an increased risk of developing nonunion fractures. Hormonal factors and cell-intrinsic mechanisms are suggested to drive these sexual dimorphisms, although underlying molecular mechanisms are still a matter of debate. Here, we observed a decreased capacity of calvarial bone recovery in female rats and a profound sexually dimorphic osteogenic differentiation in human adult neural crest-derived stem cells (NCSCs).

Impact of Contrast Enhancement and Virtual Monoenergetic Image Energy Levels on Emphysema Quantification: Experience With Photon-Counting Detector Computed Tomography.

Purpose: The aim of this study was to evaluate the impact of contrast enhancement and different virtual monoenergetic image energies on automatized emphysema quantification with photon-counting detector computed tomography (PCD-CT).

Material And Methods: Sixty patients who underwent contrast-enhanced chest CT on a first-generation, clinical dual-source PCD-CT were retrospectively included. Scans were performed in the multienergy (QuantumPlus) mode at 120 kV with weight-adjusted intravenous contrast agent.

The small-molecule protein ligand interface stabiliser E7820 induces differential cell line specific responses of integrin α2 expression.

Background: The mechanism of small-molecule stabilised protein-protein interactions is of growing interest in the pharmacological discovery process. A plethora of different substances including the aromatic sulphonamide E7820 have been identified to act by such a mechanism. The process of E7820 induced CAPERα degradation and the resultant transcriptional down regulation of integrin α2 expression has previously been described for a variety of different cell lines and been made responsible for E7820's antiangiogenic activity.

Spongostan Leads to Increased Regeneration of a Rat Calvarial Critical Size Defect Compared to NanoBone and Actifuse.

Bone substitute materials are becoming increasingly important in oral and maxillofacial surgery. Reconstruction of critical size bone defects is still challenging for surgeons. Here, we compared the clinically applied organic bone substitute materials NanoBone (nanocrystalline hydroxyapatite and nanostructured silica gel; = 5) and Actifuse (calcium phosphate with silicate substitution; = 5) with natural collagen-based Spongostan™ (hardened pork gelatin containing formalin and lauryl alcohol; = 5) in bilateral rat critical-size defects (5 mm diameter).

The heparan sulfate proteoglycan Syndecan-1 influences local bone cell communication via the RANKL/OPG axis.

The heparan sulfate proteoglycan Syndecan-1, a mediator of signals between the extracellular matrix and cells involved is able to interact with OPG, one of the major regulators of osteoclastogenesis. The potential of osteoblasts to induce osteoclastogenesis is characterized by a switch of OPG (low osteoclastogenic potential) towards RANKL production (high osteoclastogenic potential). In the present study, we investigated the influence of endogenous Syndecan-1 on local bone-cell-communication via the RANKL/OPG-axis in murine osteoblasts and osteoclasts in wild type and Syndecan-1 lacking cells.

Microsurgical reconstruction affects the outcome in a translational mouse model for Achilles tendon healing.

Background: Animal models are one of the first steps in translation of basic science findings to clinical practice. For tendon healing research, transgenic mouse models are important to advance therapeutic strategies. However, the small size of the structures complicates surgical approaches, histological assessment, and biomechanical testing.

Increased Collagen Turnover Impairs Tendon Microstructure and Stability in Integrin α2β1-Deficient Mice.

Integrins are a family of transmembrane proteins, involved in substrate recognition and cell adhesion in cross-talk with the extra cellular matrix. In this study, we investigated the influence of integrin α2β1 on tendons, another collagen type I-rich tissue of the musculoskeletal system. Morphological, as well as functional, parameters were analyzed in vivo and in vitro, comparing wild-type against integrin α2β1 deficiency.

Bone Regeneration: A Novel Osteoinductive Function of Spongostan by the Interplay between Its Nano- and Microtopography.

Scaffold materials for bone regeneration are crucial for supporting endogenous healing after accidents, infections, or tumor resection. Although beneficial impacts of microtopological or nanotopological cues in scaffold topography are commonly acknowledged, less consideration is given to the interplay between the microscale and nanoscale. Here, micropores with a 60.

Modulation of Transient Receptor Potential Channels 3 and 6 Regulates Osteoclast Function with Impact on Trabecular Bone Loss.

Enhanced osteoclast formation and function is a fundamental cause of alterations to bone structure and plays an important role in several diseases impairing bone quality. Recent work revealed that TRP calcium channels 3 and 6 might play a special role in this context. By analyzing the bone phenotype of TRPC6-deficient mice we detected a regulatory effect of TRPC3 on osteoclast function.

Cryopreservation of tendon tissue using dimethyl sulfoxide combines conserved cell vitality with maintained biomechanical features.

Biomechanical research on tendon tissue evaluating new treatment strategies to frequently occurring clinical problems regarding tendon degeneration or trauma is of expanding scientific interest. In this context, storing tendon tissue deep-frozen is common practice to collect tissue and analyze it under equal conditions. The commonly used freezing medium, phosphate buffered saline, is known to damage cells and extracellular matrix in frozen state.

CD4 virtual memory: Antigen-inexperienced T cells reside in the naïve, regulatory, and memory T cell compartments at similar frequencies, implications for autoimmunity.

It is widely accepted that central and effector memory CD4 T cells originate from naïve T cells after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true the diversity of T cell receptor (TCR) sequences within the naïve T cell compartment should be far greater than that of the memory T cell compartment, which is not supported by TCR sequencing data. Here we demonstrate that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing the same TCR sequence as their younger counterparts.

International consensus criteria for the diagnosis of Raynaud's phenomenon.

Vasoconstriction accompanied by changes in skin color is a normal physiologic response to cold. The distinction between this normal physiology and Raynaud's phenomenon (RP) has yet to be well characterized. In anticipation of the 9th International Congress on Autoimmunity, a panel of 12 RP experts from 9 different institutes and four different countries were assembled for a Delphi exercise to establish new diagnostic criteria for RP.

Age-related bone deterioration is diminished by disrupted collagen sensing in integrin α2β1 deficient mice.

Collagen binding integrins are of essential importance in the crosstalk between cells and the extracellular matrix. Integrin α2β1 is a major receptor for collagen I, the most abundant protein in bone. In this study we show for the first time that integrin α2 deficiency is linked to collagen type I expression in bone.

Procollagen C-proteinase enhancer grasps the stalk of the C-propeptide trimer to boost collagen precursor maturation.

Tight regulation of collagen fibril deposition in the extracellular matrix is essential for normal tissue homeostasis and repair, defects in which are associated with several degenerative or fibrotic disorders. A key regulatory step in collagen fibril assembly is the C-terminal proteolytic processing of soluble procollagen precursors. This step, carried out mainly by bone morphogenetic protein-1/tolloid-like proteinases, is itself subject to regulation by procollagen C-proteinase enhancer proteins (PCPEs) which can dramatically increase bone morphogenetic protein-1/tolloid-like proteinase activity, in a substrate-specific manner.

Procollagen C-proteinase enhancer stimulates procollagen processing by binding to the C-propeptide region only.

Bone morphogenetic protein-1 (BMP-1) and the tolloid-like metalloproteinases control several aspects of embryonic development and tissue repair. Unlike other proteinases whose activities are regulated mainly by endogenous inhibitors, regulation of BMP-1/tolloid-like proteinases relies mostly on proteins that stimulate activity. Among these, procollagen C-proteinase enhancers (PCPEs) markedly increase BMP-1/tolloid-like proteinase activity on fibrillar procollagens, in a substrate-specific manner.

Processing of procollagen III by meprins: new players in extracellular matrix assembly?

Meprins α and β, a subgroup of zinc metalloproteinases belonging to the astacin family, are known to cleave components of the extracellular matrix, either during physiological remodeling or in pathological situations. In this study we present a new role for meprins in matrix assembly, namely the proteolytic processing of procollagens. Both meprins α and β release the N- and C-propeptides from procollagen III, with such processing events being critical steps in collagen fibril formation.