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Endochondral ossification is the process where cartilage forms prior to ossification and in which new bone forms during both fracture healing and ectopic bone formation. Transitioning to ossification is a highly coordinated process between hypertrophic chondrocytes, vascular endothelial cells, osteoblasts and osteoclasts. A critical biological process that is central to the interactions of these various...
The zebrafish is a powerful experimental model to investigate the genetic and morphologic basis of vertebrate development. Analysis of skeletogenesis in this fish is challenging as a result of the small size of the developing and adult zebrafish. Many of the bones of small fishes such as the zebrafish and medaka are quite thin, precluding many standard assays of bone quality and morphometrics commonly...
Paget's disease of bone (PDB) is marked by the focal activity of abnormal osteoclasts (OCLs) with excess bone resorption. We previously detected measles virus nucleocapsid protein (MVNP) transcripts in OCLs from patients with PDB. Also, MVNP stimulates pagetic OCL formation in vitro and in vivo. However, the mechanism by which MVNP induces excess OCLs/bone resorption activity in PDB is unclear. Microarray...
Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. OPN is a well-known inhibitor of matrix mineralization, and enzymatic modification of OPN can affect this inhibitory function. In bone, OPN exists both as a monomer and as a high-molecular-weight polymer – the latter is formed by transglutaminase-mediated...
WNT signaling plays a major role in bone and cartilage metabolism. Impaired WNT/β-catenin signaling leads to early-onset osteoporosis, but specific features in bone and other tissues remain inadequately characterized. We have identified two large Finnish families with early-onset osteoporosis due to a heterozygous WNT1 mutation c.652T>G, p.C218G. This study evaluated the impact of impaired WNT/β-catenin...
Opposite to the fracture side, bone mineral density (BMD) measured by DXA at the contra-lateral side does not change after a distal radius fracture. However, it is unknown if also bone micro-architecture and strength at the contralateral side are unaffected. Therefore, the aim of this study was to assess BMD, micro-architecture and bone mechanical properties at the contra-lateral side during two years...
Osteoporotic vertebral fractures (VFs) are often misdiagnosed because asymptomatic and occurring in the absence of specific trauma. Further, diagnostic assessment of VFs may be suboptimal.To assess the misdiagnosis of vertebral fractures on local radiographic readings in the cohort of patients enrolled in the POINT study.We enrolled hospitalised patients, admitted for any cause to the Internal Medicine...
Individuals differ in forearm length. As microstructure differs along the radius, we hypothesized that errors may occur when sexual and racial dimorphisms are quantified at a fixed distance from the radio-carpal joint.Microstructure was quantified ex vivo in 18 cadaveric radii using high resolution peripheral quantitative computed tomography and in vivo in 158 Asian and Caucasian women and men at...
Proteomic analysis of extracellular matrices (ECM) of dentoalveolar tissues can provide insights into developmental, pathological, and reparative processes. However, targeted dissection of mineralized tissues, dental cementum (DC), alveolar bone (AB), and dentin (DE), presents technical difficulties. We demonstrate an approach combining EDTA decalcification and laser capture microdissection (LCM),...
Small vertebral size is an independent risk factor for osteoporotic vertebral fractures. Physical growth in early life is related to bone health in later life, but the relationship of early growth versus vertebral size has been inconclusively studied. Utilizing the Northern Finland Birth Cohort 1966 with a 47-year follow-up, we investigated how physical growth in early life is associated with midlife...
Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder and is classified as one of the ciliopathy. The patients manifest a characteristic craniofacial dysmorphology but the effects of Bbs3 deficiency in the developmental process during the craniofacial pathogenesis are still incompletely understood. Here, we analyzed a cranial development of a BBS model Bbs3−/− mouse. It was previously reported...
Berardinelli–Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty in storing lipids in adipocytes, low body fat mass, hypoleptinemia, and hyperinsulinemia. Sclerostin is a product of SOST gene that blocks the Wnt/β-catenin pathway, decreasing bone formation and enhancing adipogenesis. There are no data about sclerostin in people with BSCL.We aimed...
Interleukin (IL)-17 is crucial to osteoclast differentiation and activation. Osteocytes support osteoclast formation and are thought to orchestrate bone remodeling in response to fluid flow. The contribution of IL-17 to osteocyte-related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4 cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It was the first...
Macrophages are important phagocytosing and cytokine producing cells with effects on fracture healing. We used clodronate-containing liposomes to reduce the number of macrophages, in order to study their role in the early phases of cancellous bone healing.Holes were drilled bilaterally into the cancellous bone of the proximal metaphysis of the tibia of 60 mice. A screw was inserted in the hole in...
Bone remodeling is a tightly regulated process influenced by chemokines. ACKR2 is a decoy receptor for CC chemokines functioning as regulator of inflammatory response. In this study we investigated whether the absence of ACKR2 would affect bone phenotype and remodeling induced by mechanical loading.An orthodontic appliance was placed between incisors and first molar of ACKR2 deficient (ACKR2−/−) and...
Osteoporosis is one of the most common diseases worldwide. In osteoporosis, vertebral fractures represent a major burden. Lipoxygenase (LOX) inhibitors such as baicalein and zileuton may represent a promising therapeutic option owing to their antioxidative effects and suppression of various inflammatory processes in muscle and bone. The effect of these LOX inhibitors on the spine was studied in osteopenic...
Parity has been suggested as a possible factor affecting bone health in women. However, study results on its association with bone mineral density are conflicting.PubMed, EMBASE, the Cochrane Library, and Korean online databases were searched using the terms “parity” and “bone mineral density”, in May 2016. Two independent reviewers extracted the mean and standard deviation of bone mineral density...
Bone fracture risk assessed ancillary to positron emission tomography with computed tomography co-registration (PET/CT) could provide substantial clinical value to oncology patients with elevated fracture risk without introducing additional radiation dose. The purpose of our study was to investigate the feasibility of obtaining valid measurements of bone mineral density (BMD) and finite element analysis-derived...
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