Bone Abstracts

Delayed fracture healing is frequently experienced in patients with systemic inflammation such as during rheumatoid arthritis (RA). The reasons for this are diverse, but could also be caused by inflammatory cytokines and/or growth factors in serum from patients with active disease. We hypothesized that serum from patients with active RA contains circulating inflammatory factors that inhibit differentiation of osteochondrogenic precursors.Serum was obtain...

Dietary Ca insufficiency is a common finding, independently of socio-economic status. A low Ca intake (CaI) increases bone turnover leading to bone loss. This effect becomes more important during estrogen withdrawing. We previously found that a mixture of galactooligosaccharides (GOS) and fructooligosaccharides (FOS) enhances Ca and P absorption (Abs), being a suitable tool to optimize its bioavailability and consequently bone health. The present study evaluated the effect of ...

Mast cells (MCs) are pro-inflammatory sensor and effector cells of the immune system. MCs seem to play a role in bone metabolism, because patients with systemic mastocytosis develop osteoporosis. MCs are present in the fracture callus during bone healing, however, their function has not yet been investigated. Here, we examined the role of MCs in the inflammatory and repair phase during fracture healing.Male 12-week old MC deficient mice (Mcpt5-Cre R-DTA)...

Transcript therapies, using chemically modified messenger RNAs (cmRNAs), are emerging as safer yet promising substitutes for gene and recombinant protein therapies. However, their applications have been limited due to transient translation and relative low stability of cmRNAs, compared to DNAs. Here we showed that vacuum-dried cmRNA-loaded collagen sponges, so called Transcript-Activated Matrices (TAMs), could serve as depots for sustained cmRNA delivery, providing steady stat...

Delivery of recombinant human bone morphogenetic protein (rhBMP2) with various carriers has been showing the successful induction of bone formation in many bony defects, including oral and maxillofacial regions. However, effectiveness of the exogenous proteins, when repeatedly administered into different regions in an individual, has not been determined. The present study was aimed to examine alterations of ectopic or orthotopic bone generation and serum level of anti-BMP2 ant...

The aim of this study was to investigate the biocompatibility of hydroxyapatite (HAP) powder from whitemouth croaker fish (Micropogonias furnieri). For this purpose, fragments from HAP with 0.5 cm2 were inserted in the subcutaneous tissue of animals. After 7, 15, and 30 days, histopathological analysis was performed. The results showed that it was possible to detect tissue reactions closely related to cytotoxicity in a time-exposure manner. At day 7, modera...

Objective: The purpose of this study is to investigate the effects of the combined teriparatide (TPTD) and denosumab (DMAB) on both cortical and cancellous bone regeneration.Materials and methods: Bone defects were created in the diaphysis of the right femur and in the epimetaphysis of the left femur in 8-week old female C57/BL6N mice. After making bone defects, Mice were given either saline or 40 μg/kg TPTD for 20 days (5× per week) and were s...

Introduction: A synthetic prostacyclin IP receptor agonist (ONO-1301) has been reported to induce the production of endogenous HGF and VEGF in fibroblasts by stimulating cAMP production.Materials and methods: In vitro; murine primary osteoblasts and cell line (ST2, MC3T3-E1, C2C12) were treated with BMP-2 (0–100 ng/ml) and ONO-1301 (0–10−6 M). ALP assay and cell proliferation assay were performed. In vivo analysis, Col...

Mammalian target of rapamycin (mTOR) functions mainly in the form of two complexes, namely mTORC1 and mTORC2, which are distinct in their unique components, raptor and rictor. Here, we focused on bone phenotypes in mice with a specific deletion of rictor using a Cre recombinase gene whose expression was driven by the promoter of osteocalcin. All procedures involving mice were approved by the Institutional Animal Care and Use Committee of the local admin. DXA analysis showed a ...

Introduction: Indirect inhibition of the extracellular BMP antagonist network and the activation of Wnt signaling by PTH1-34 suggest the possibility of synergistic effect on bone regeneration by the co-administration of BMP and PTH1-34.Materials and methods: In a rat critical-sized femoral defect (7 mm) model, SD rats (n=32) were operated by absorbable collagen sponge containing two different BMP-2 dosage treatments; 1) 2 μg (low dose) and ...

In this study, we evaluated the effect of the association of a bioactive glass-ceramic scaffold (Biosca) with mesenchymal stem cells derived from either bone marrow (BM-MSCs) or adipose tissue (AT-MSCs) on bone formation in calvarial defects of osteoporotic rats. Wistar rats were submitted to bilateral ovariectomy (OVX) or only to the surgical stress (Sham), under approval of the Committee of Ethics in Animal Research. After 5 months, 5-mm unilateral calvarial defect was creat...

Interleukin-6 (IL-6) plays an important role in bone metabolism and regulates fracture healing in a presently unknown process. In the fracture callus IL-6 expression is biphasic; it peaks during the inflammatory phase and again during intramembranous and endochondral ossification (Ai-Aql et al. 2008). Few studies using IL-6 knockout mice indicate that IL-6 might be crucial for bone healing (Yang et al. 2007). However, a generalized IL-6 knockout induces multi...

Chronic calcium- and vitamin-D-deficiencies are crucial risk factors for osteoporosis. However, their significance for fracture healing is still poorly investigated, despite the clinical evidence that osteoporotic bone healing is disturbed. This study addressed the important question, whether chronic deprivation of calcium and vitamin D compromises bone repair and if this could be rescued by a supplementation post-trauma. Because clinical hints suggest that a fracture induces ...

Considering limited information on skeletal system properties in emu (Dromaius novaehollandiae), the aim of this study was to determine morphological and densitometric parameters of tarsometatarsus obtained from adult males (N=6) and females (N=7). The study was performed on birds reared at the Department of Poultry and Ornamental Bird Breeding of Western Pomeranian University of Technology in Szczecin, Poland. Male and female emu were slaughtered to obtain l...

The aim of the study was to evaluate interrelationships between morphometric, densitometric and mechanical properties of femur in ostriches (Struthio camelus). 14-month-old male and female ostriches (N=46) were slaughtered to obtain left femur for analyses. Using quantitative computed tomography (QCT) technique, volumetric bone mineral density (vBMD) of the trabecular (Td) and cortical bone (Cd) were measured. Bone mineral density (BMD) and bone mineral content (BMC) ...

There have been considerable advances in our knowledge of how loss of androgens signalling leads to bone loss in aging male with hypogonadism. However, the roles of androgen actions on the skeletal growth remain limited. Recently, new insights into the function of and androgen receptor (AR), learned from human genetic mutations and gene targeting mouse models have contributed to emerged understanding of the androgenic effects on bone and cartilage in health and diseases. Here,...

Previous studies demonstrated a negative influence of the growth- and differentiation factor midkine (MDK) on bone formation during bone remodeling and fracture healing. Additionally, MDK-deficiency protected mice from a loss of trabecular bone mass after ovariectomy (OVX). Therefore, we hypothesized that MDK may also be involved in the pathogenesis of delayed, osteoporotic fracture healing after OVX in mice. Thus, we analyzed the expression of MDK during bone regeneration and...

We used atomic force microscopy (AFM) to study the morphology and development of mineralization-competent matrix vesicles (MVs) secreted by chondrocytes isolated from WT and Phospho1−/− mice in order to validate the role of PHOSPHO1 in MV mineralization. All MVs appeared as flattened globular features either individually dispersed or connected to a mat-like structure. The mat-like structure very closely resembled type-X collagen that has been de...

The mammalian circadian clock is tightly controlled by clock genes, which have been shown to regulate up to 20% of the transcriptome in any given tissue. Evidence is accumulating that light-modulation perpetually affects circadian clock performance. In accordance, shift work or chronic jet lag is associated with higher risk of disease later in life, including osteoporosis. In this study, we assessed whether gestational jet lag in mice reduces bone mass postnatally.<p class...

The co-chaperone, Bcl-2-associated athanogene-1 (BAG-1), is expressed by chondrocytes and osteogenic cells, and interacts via heat shock chaperones (HSC70/HSP70) with diverse proteins such as nuclear hormone receptors to regulate cell proliferation, differentiation and apoptosis. Early embryonic lethality in Bag-1 null mice has limited the investigation of the function of BAG-1 in skeletal development. The present study aimed to elucidate the role of BAG-1 in skeletal...

High resolution peripheral quantitative computed tomography (HR-pQCT) in combination with micro finite element analysis (μFEA) is a promising tool to assess longitudinal changes in bone mechanical properties during the fracture healing process in the distal radius. In the present study we investigate if these changes can be detected as well when using images with lower resolutions, comparable to clinical QCT images.Postmenopausal women with a stable...

Purpose: The aim of this research was to develop an in vivo platform for conveniently examining the potential of various factors to augment chondral bone regeneration. For this purpose, we have established a de novo partial tail amputation model in adult zebrafish, which includes the resection of cartilage-template based bones from the endoskeletal caudal complex. Endoskeletal amputations were rarely studied, as opposed to those of the distal caudal fin rays, a well-e...

Background: Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density can be affected in transgender adolescents when puberty is postponed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT).Objective: To investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents.<p ...

High doses of BMPs are needed to achieve clinical success in bone fracture repair with currently available devices. BMP6 has a higher potency in stimulation of bone formation then its paralogue BMP7 due to less susceptibility to Noggin. The BMP6 carrier is a whole blood derived coagulum (WBCD) from the peripheral blood (OSTEOGROW). This WBCD, as an endogenous biocompatible material, significantly reduces the inflammatory response associated with current BMP-based treatments. M...

The purposes of this present study were to compare the osteoconductivity and absorbability in patients of open wedge high tibial osteotomy with medially gaps filled with hydroxyapatite (HA) or beta-tricalcium phosphate (β-TCP).Total 41 knees of 40 patients in whose follow up period more than 1 year were enrolled. The patients were divides into two groups, group I (22 knees, 21 patients) used HA and group II (19knees, 19 patients) used β-TCP...

Adiponectin may play a role in both bone and periodontal remodeling. In this study, the effect of repetitive local administration of human recombinant adiponectin on experimental tooth movement was examined.The first molar of 24 male Wistar rats was moved mesially by a closed coil spring ligated to the molar and anchored to the incisors in front for 14 days, with adiponectin injections every 3rd day. Amount of tooth movement was examined by feeler gauge ...

Background: Three-dimensional scaffolds for the tissue regeneration are also crucial materials for bone formation. In particular, the scaffolds must provide the space for the cell migration and new bone formation. Collagen is one of the useful scaffolds to reach these performance, however, it is not always a desired biodegradability. Recently, we succeeded in developing low adhesive scaffold type I collagen (LASCol) (patent pending) which has the ability to form fibrils. In th...

Sustained release of bone morphogeneic protein (BMP)-2 by heparin-contained biomaterials is advantageous for bone tissue regeneration using low dose BMP-2. However, its effect in high dose BMP-2 is still unclear and should be clarified considering the clinical use of high dose of BMP-2 in spine and oral surgery. This study aimed to evaluate the efficacy of heparin-conjugated collagen sponge (HCS) in high dose BMP-2 delivery by investigating in vivo initial osteogenic regulatio...

The healing of skeletal fractures involves a cascade of overlapping cellular events. This study aims to deepen the understanding of molecular networks orchestrating these events.Standard closed fracture in the left femur of male 8–10 weeks old C57BL/6N mice were analyzed at (day=D) D3, D7, D10, D14, D21 & D28 post fracture (N=5/time point). Total RNA was prepared for whole genome expression profiling using Illumina μ-array kit. Dat...

Bone fractures of patients suffering from type 2 diabetes mellitus (T2DM) represent an emerging socioeconomic problem. Underling mechanisms are poorly understood and therapies are limited. Our previous studies have shown that sulfated hyaluronan (sHA3) suppresses osteoclast activity while supporting osteoblast function in vitro. Hence, we now investigated if sHA3 can improve the delayed fracture healing in rats with T2DM.Porous, cross-linked lactide-base...

Non-healing fractures caused by trauma, disease or tumour resection demand the use of bone grafts to support and stimulate the healing process. We sought to develop and evaluate the effect of a novel bioactive biodegradable biomaterial designed to fill large bone lesions and to improve bone healing. We used two-photon polymerised synthetic polymer scaffolds composed of lactide (LA), caprolactone (CL), and methacrylate (MA) with varying LA: CL ratio and percentage of methacryla...

Aim: Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) is an invasive treatment able to control local disease and pain of bone tumors. Unfortunately, there is not any scientific evidence of the biological effect of MRgFUS treatment on tumor cells, especially in lower dose region, where tissues are only warmed to sub-lethal temperatures. Here we investigate the effect of in vitro MRgFUS treatment, at different levels of acoustic energy (200–630 J), on ...

Periosteum contains mesenchymal progenitors and is essential for fracture healing. Signaling mechanisms governing periosteal reaction to injury remain largely unidentified. We previously investigated how PI3 kinase signaling affects the skeletal system using CblYF/YF knock-in (YF) mice wherein PI3K signaling is perturbed by abolition of interaction between Cbl, an E3 ubiquitin-ligase/adaptor protein, and p85 subunit of PI3K. YF mice displayed increased bone volume u...

Introduction: Research on biomaterials for bone regeneration generates a plethora of new biomaterials requiring evaluation with reliable and comparable methods of biocompatibility and functionality for clinical translation. To reduce the burden of in vivo assessment, there is a need for refined in vitro assays that are predictive of in vivo outcomes. This retrospective study correlated in vitro results with in vivo outcomes observed...

We have previously shown that female neuronal nitric oxide synthase knockout (nNOS KO) mice have increased trabecular bone volume. However, this study was performed in mice at 10 weeks of age only. To investigate whether the high bone volume is maintained during ageing, we compared 3-month- and 12-month-old wild type (WT) and nNOS KO mice using μCT. The tibias from 8 WT and 8 nNOS KO mice at each age were dissected, fixed for 24 h in buffered formalin, stored in 70% ethan...