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Yun Bai, Chuan Liu, Lei Fu, Xiaoshan Gong, Ce Dou, Zhen Cao, Hongyu Quan, Jianmei Li, Fei Kang, Jingjin Dai, Chunrong Zhao, Shiwu Dong
Endochondral ossification is crucial for bone formation in both adult bone repair process and embryo long-bone development. In endochondral ossification, bone marrow-derived mesenchymal stem cells (BMSCs) first differentiate to chondrocyte, BMSC-derived chondrocyte then endure a hypertrophic process to generate new bone. Endochondral ossification-based bone repair is a promising strategy to cure massive bone defect, which is a major clinical issue in orthopedics. However, challenges still remain for this novel strategy...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yubo Sun, Alex J Kiraly, Michael Cox, David R Mauerhan, Edward N Hanley
Phosphocitrate (PC) and its analogue, PC-β ethyl ester, inhibit articular cartilage degeneration in Hartley guinea pigs. However, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the hypothesis that PC exerted its disease-modifying effect on osteoarthritis (OA), in part, by inhibiting a molecular program similar to that in the endochondral pathway of ossification. The results demonstrated that severe proteoglycan loss occurred in the superficial and middle zones, as well as in the calcified zone of articular cartilage in the Hartley guinea pigs...
April 2018: Experimental and Therapeutic Medicine
Virginia Piombo, Katja Jochmann, Daniel Hoffmann, Manuela Wuelling, Andrea Vortkamp
Multiple osteochondromas (MO) syndrome is a dominant autosomal bone disorder characterized by the formation of cartilage-capped bony outgrowths that develop at the juxtaposition of the growth plate of endochondral bones. MO has been linked to mutations in either EXT1 or EXT2, two glycosyltransferases required for the synthesis of heparan sulfate (HS). The establishment of mouse mutants demonstrated that a clonal, homozygous loss of Ext1 in a wild type background leads to the development of osteochondromas. Here we investigate mechanisms that might contribute to the variation in the severity of the disease observed in human patients...
March 12, 2018: Bone
Xin Wang, Yi Zhang, Wenjun Ji, Jun Ao
Fracture hematoma formation describes a transitional phase that involves a dynamic and tightly choreographed interaction between the fibrin matrix, cells, and cytokines that guides the ensuing bone repair. Here we propose a novel hypothesis to explain why hematomas in conjunction with critical sized bone defects are prone to differentiate into fibrous tissues, which eventually results in non-unions of the bone. We postulate that certain hematoma qualities are triggers that influence cell biological behaviours and that the release of certain growth factors determines what pattern of remodelling will prevail: intramembranous or endochondral ossification...
April 2018: Medical Hypotheses
Yung-Ching Chen, King-Chuen Wu, Bu-Miin Huang, Edmund Cheung So, Yang-Kao Wang
Midazolam, a benzodiazepine derivative, is widely used for sedation and surgery. However, previous studies have demonstrated that Midazolam is associated with increased risks of congenital malformations, such as dwarfism, when used during early pregnancy. Recent studies have also demonstrated that Midazolam suppresses osteogenesis of mesenchymal stem cells (MSCs). Given that hypertrophic chondrocytes can differentiate into osteoblast and osteocytes and contribute to endochondral bone formation, the effect of Midazolam on chondrogenesis remains unclear...
March 7, 2018: Journal of Cellular and Molecular Medicine
Riko Nishimura, Kenji Hata, Eriko Nakamura
Chondrocytes, which are originated from undifferentiated mesenchymal stem cells, play roles in skeletal development and growth in mammal, and smooth movement of joints. Endochondral ossification is necessary for skeletal development, and the multiple and complex biological events are precisely regulated by several hormones, cytokines, and their downstream signaling and transcriptional regulation. On the other hands, articular chondrocytes physiologically retains their features during a lifetime. Numerous molecules involved in endochondral ossification have been identified and investigation of the molecular mechanisms have amazingly progressed...
2018: Clinical Calcium
Hiroki Goto, Miki Nishio, Yoko To, Tatsuya Oishi, Yosuke Miyachi, Tomohiko Maehama, Hiroshi Nishina, Haruhiko Akiyama, Tak Wah Mak, Yuma Makii, Taku Saito, Akihiro Yasoda, Noriyuki Tsumaki, Akira Suzuki
Hippo signaling is modulated in response to cell density, external mechanical forces, or rigidity of the extracellular matrix (ECM). The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and have important effects on Yes-associated protein-1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which are potent transcriptional regulators. YAP1/TAZ are key contributors to cartilage and bone development but the molecular mechanisms by which the Hippo pathway controls chondrogenesis are largely unknown...
March 6, 2018: Development
Chen Zhao, Wei Jiang, Nian Zhou, Junyi Liao, Mingming Yang, Ning Hu, Xi Liang, Wei Xu, Hong Chen, Wei Liu, Lewis L Shi, Leonardo Oliveira, Jennifer Moriatis Wolf, Sherwin Ho, Aravind Athiviraham, H M Tsai, Tong-Chuan He, Wei Huang
Cartilage injuries caused by arthritis or trauma pose formidable challenges for effective clinical management due to the limited intrinsic proliferative capability of chondrocytes. Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries. Bone morphogenetic protein 2 (BMP2) induces effective chondrogenesis of mesenchymal stem cells (MSCs) and can thus be explored as a potential therapeutic agent for cartilage defect repair...
December 2017: Genes & Diseases
Marja Steenman, Olivier Espitia, Blandine Maurel, Beatrice Guyomarch, Marie-Françoise Heymann, Marc-Antoine Pistorius, Benjamin Ory, Dominique Heymann, Rémi Houlgatte, Yann Gouëffic, Thibaut Quillard
Calcification is independently associated with cardiovascular events and morbidity. The calcification burden in atherosclerotic lesions quantitatively and qualitatively differs between arterial beds. Cardiovascular risk factors (CVRF) differentially affect plaque development between arterial beds. The aim of this study was to evaluate the impact of CVRF on atherosclerotic plaque calcification and to further study the molecular arterial heterogeneity that could account for these differences. Histological analysis was performed on atherosclerotic plaques from 153 carotid, 97 femoral and 28 infrapopliteal arteries...
March 2, 2018: Scientific Reports
Hongyang Zhang, Xiaojuan Shi, Long Wang, Xiaojie Li, Chao Zheng, Bo Gao, Xiaolong Xu, Xisheng Lin, Jinpeng Wang, Yangjing Lin, Jun Shi, Qiang Huang, Zhuojing Luo, Liu Yang
A fracture is the most dangerous complication of osteoporosis in patients because the associated disability and mortality rates are high. Osteoporosis impairs fracture healing and prognosis, but how intramembranous ossification (IO) or endochondral ossification (EO) during fracture healing are affected and whether these two kinds of ossification are different between glucocorticoid-induced osteoporosis (GIOP) and estrogen deficiency-induced osteoporosis (EDOP) are poorly understood. In this study, we established two bone repair models that exhibited repair via IO or EO and compared the pathological progress of each under GIOP and EDOP...
March 1, 2018: Scientific Reports
Shu-Cheng Huang, Li-Hong Zhang, Jia-Lu Zhang, Mujeeb Ur Rehman, Xiao-le Tong, Gang Qiu, Xiong Jiang, Mujahid Iqbal, Muhammad Shahzad, Yao-Qin Shen, Jia-Kui Li
Tibial dyschondroplasia (TD) is the most-prevalent leg disorder in fast-growing chickens; it is intractable and characterized by abnormal endochondral bone formation of proximal tibial growth-plates (TGPs). Previous studies have shown that bone is a highly vascularized tissue dependent on the coordinated coupling between angiogenesis and osteogenesis, but the underlying mechanisms of bone formation and bone remodeling are poorly defined in TD chickens. Here, we observed that inhibition of vasculogenesis and angiogenesis remarkably impaired vascular invasion in the hypertrophic chondrocyte zone of the TGPs, resulting in the massive death of chondrocytes due to a shortage of blood vessels and nutrients...
February 27, 2018: Scientific Reports
I A Otto, R Levato, W R Webb, I M Khan, C C Breugem, J Malda
Paramount for the generation of auricular structures of clinically-relevant size is the acquisition of a large number of cells maintaining an elastic cartilage phenotype, which is the key in producing a tissue capable of withstanding forces subjected to the auricle. Current regenerative medicine strategies utilize chondrocytes from various locations or mesenchymal stromal cells (MSCs). However, the quality of neo-tissues resulting from these cell types is inadequate due to inefficient chondrogenic differentiation and endochondral ossification, respectively...
February 27, 2018: European Cells & Materials
Yan Jing, Junjun Jing, Ke Wang, Kevin Chan, Stephen E Harris, Robert J Hinton, Jian Q Feng
A recent breakthrough showing that direct trans-differentiation of chondrocytes into bone cells commonly occurs during endochondral bone formation in the growth plate, articular cartilage, and mandibular condylar cartilage suggests that chondrogenesis and osteogenesis are likely one continuous biological process instead of two separate processes. Yet, gene regulation of this cell transformation is largely unclear. Here, we employed cartilage-specific β-catenin loss-of-function ( β-cateninfx/fx ) and gain-of-function ( β-cateninfx(exon3)/ fx(exon3) ) models in the R26R Tomato background (for better tracing the cell fate of chondrocytes) to study the role of β-catenin in cell trans-differentiation...
2018: International Journal of Biological Sciences
Yasmin D Hailer, Nils P Hailer
BACKGROUND: Osteochondrosis includes numerous diseases that occur during rapid growth, characterized by disturbances of endochondral ossification. One example, Legg-Calvé-Perthes disease, is characterized by disruption of the blood supply to the femoral head epiphysis, and a systemic etiology often has been suggested. If this were the case, secondary osteochondroses at locations other than the hip might be expected to be more common among patients with Legg-Calvé-Perthes disease, but to our knowledge, this has not been evaluated in a nationwide sample...
February 23, 2018: Clinical Orthopaedics and related Research
Anara Karaca, Vijayram Reddy Malladi, Yan Zhu, Olta Tafaj, Elena Paltrinieri, Joy Y Wu, Qing He, Murat Bastepe
GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth...
February 20, 2018: Bone
Yasuhiko Bando, Hide Sakashita, Fuyoko Taira, Genki Miyake, Yudai Ogasawara, Koji Sakiyama, Yuji Owada, Osamu Amano
Septoclasts are mononuclear spindle-shaped phagocytes with their long processes in uncalcified cartilage matrices and locate adjacent to the capillary endothelium at the chondro-osseous junction of the growth plate. We have previously revealed a selective expression of epidermal-type fatty acid-binding protein (E-FABP/FABP5) in septoclasts. Although, pericytes are known to distribute along capillaries and directly surround their endothelial cells in a situation similar to septoclasts, no clear evidence is available on the relationship between septoclasts and pericytes...
February 20, 2018: Histochemistry and Cell Biology
Morgan Jones, Lee Breakwell, Ashley Cole, Paul Arundel, Nick Bishop
PURPOSE: The objective of this article is to report a case of type V osteogenesis imperfecta (OI) undergoing posterior instrumented fusion for scoliosis. Type V OI is a moderately severe dysplasia causing primary defects in endochondral bone ossification or mineralisation. It is characterised by hyperplastic callus (HPC) formation, interosseous membrane calcifications, poor bone quality and spinal deformities including scoliosis. Data on the surgical management of spinal deformities in this patient group are lacking...
February 19, 2018: European Spine Journal
Yogesh Kumar, Tathagata Biswas, Gatha Thacker, Jitendra Kumar Kanaujiya, Sandeep Kumar, Anukampa Shukla, Kainat Khan, Sabyasachi Sanyal, Naibedya Chattopadhyay, Amitabha Bandyopadhyay, Arun Kumar Trivedi
During endochondral ossification, cartilage template is eventually replaced by bone. This process involves several well characterised, stereotypic, molecular and cellular changes in the cartilage primordia. These steps involve transition from resting to proliferative and then pre-hypertrophic to finally hypertrophic cartilage. BMP signaling is necessary and sufficient for osteogenesis. However, the specific step(s) of endochondral ossification in which BMP signaling plays an essential role is not yet known...
February 13, 2018: Free Radical Biology & Medicine
Dan Lin, Yanjun Chai, Yifan Ma, Bing Duan, Yuan Yuan, Changsheng Liu
Initiation of endogenous repair mechanisms, including key steps of stem cell recruitment and cartilage intermediate formation in endochondral ossification, is vital to regeneration of large bone defects. To biomimetically promote a rapid initiation and ensuing osteogenic stimulation, exogenous chemokine IL-8 and growth factor BMP-2 were orchestrated in a mesoporous bioactive glass (MBG)-based spatiotemporal delivery system, to achieve a rapid release of IL-8 followed by a long-term sustained release of BMP-2...
November 17, 2017: Biomaterials
Markus Linder, Manfred Hecking, Elisabeth Glitzner, Karin Zwerina, Martin Holcmann, Latifa Bakiri, Maria Grazia Ruocco, Jan Tuckermann, Georg Schett, Erwin F Wagner, Maria Sibilia
Mice deficient in epidermal growth factor receptor (Egfr-/- mice) are growth retarded and exhibit severe bone defects that are poorly understood. Here we show that EGFR-deficient mice are osteopenic and display impaired endochondral and intramembranous ossification resulting in irregular mineralization of their bones. This phenotype is recapitulated in mice lacking EGFR exclusively in osteoblasts, but not in mice lacking EGFR in osteoclasts indicating that osteoblasts are responsible for the bone phenotype...
February 14, 2018: Cell Death and Differentiation
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