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Yu Yan, Xin Cheng, Ren-Hao Yang, He Li, Jian-Long Chen, Zheng-Lai Ma, Guang Wang, Manli Chuai, Xuesong Yang
Phenobarbital is an antiepileptic drug that is widely used to treat epilepsy in a clinical setting. However, a long term of phenobarbital administration in pregnant women may produce side effects on embryonic skeletogenesis. In this study, we aim to investigate the mechanism by which phenobarbital treatment induces developmental defects in long bones. We first determined that phenobarbital treatment decreased chondrogenesis and inhibited the proliferation of chondrocytes in chick embryos. Phenobarbital treatment also suppressed mineralization in both in vivo and in vitro long bone models...
2016: Frontiers in Pharmacology
Paul Kostenuik, Faisal M Mirza
Delayed healing and nonunion of fractures represent enormous burdens to patients and healthcare systems. There are currently no approved pharmacological agents for the treatment of established nonunions, or for the acceleration of fracture healing, and no pharmacological agents are approved for promoting the healing of closed fractures. Yet several pharmacologic agents have the potential to enhance some aspects of fracture healing. In preclinical studies, various agents working across a broad spectrum of molecular pathways can produce larger, denser and stronger fracture calluses...
October 15, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Weiguang Wang, Buer Song, Teni Anbarchian, Anna Shirazyan, Joshua E Sadik, Karen M Lyons
TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO), global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes...
October 2016: PLoS Genetics
Leilei Zhong, Xiaobin Huang, Emilie Dooms Rodrigues, Jeroen Leijten, Theo Verrips, Mohamed El Khattabi, Marcel Karperien, Janine N Post
Hypertrophic differentiation occurs during in vitro chondrogenesis of mesenchymal stem cells (MSCs), decreasing the quality of the cartilage construct. Previously we identified WNT pathway antagonists Dickkopf 1 homolog (DKK1) and frizzled-related protein (FRZB) as key factors in blocking hypertrophic differentiation of hMSCs. In this study, we investigated the role of endogenously expressed DKK1 and FRZB in chondrogenesis of hMSC, chondrocyte redifferentiation and in preventing cell hypertrophy using three relevant human cell based systems, isolated hMSCs, isolated primary human chondrocytes (hChs), and co-cultures of hMSCs with hChs for which we specifically designed neutralizing nano-antibodies...
October 12, 2016: Stem Cells and Development
Xuan Wen, Xiaogang Li, Yubing Tang, Junzhou Tang, Siru Zhou, Yangli Xie, Jingyuan Guo, Jing Yang, Xiaolan Du, Nan Su, Lin Chen
Chondrogenesis can regulate bone formation. Fibroblast growth factor receptor 3, highly expressed in chondrocytes, is a negative regulator of bone growth. To investigate whether chondrocyte FGFR3 regulates osteogenesis, thereby contributing to postnatal bone formation and bone remodeling, mice with conditional knockout of Fgfr3 in chondrocytes (mutant, MUT) were generated. MUT mice displayed overgrowth of bone with lengthened growth plates. Bone mass of MUT mice was significantly increased at both 1 and 4 months of age...
October 11, 2016: Journal of Biological Chemistry
Christoph Meinert, Karsten Schrobback, Peter A Levett, Cameron Lutton, Robert L Sah, Travis J Klein
Biological tissues at articulating surfaces, such as articular cartilage, typically have remarkable low-friction properties that limit tissue shear during movement. However, these frictional properties change with trauma, aging, and disease, resulting in an altered mechanical state within the tissues. Yet, it remains unclear how these surface changes affect the behaviour of embedded cells when the tissue is mechanically loaded. Here, we developed a cytocompatible, bilayered hydrogel system that permits control of surface frictional properties without affecting other bulk physicochemical characteristics such as compressive modulus, mass swelling ratio, and water content...
October 8, 2016: Acta Biomaterialia
Tommy A Karlsen, Gustavo Antonio de Souza, Bjørn Ødegaard, Lars Engebretsen, Jan E Brinchmann
Osteoarthritis is a serious disease of articular cartilage. The pathogenic factors contributing to this disorder are inflammation, extracellular matrix degradation and failure to rebuild the articular cartilage. Preclinical studies suggest that microRNA-140 may play a protective role in osteoarthritis development, but little is known about the mechanism by which this occurs. Here we present the results of forced expression of microRNA-140 in an in vitro model of osteoarthritis, evaluated by global proteomics analysis...
October 11, 2016: Molecular Therapy. Nucleic Acids
Murong You, Juehua Jing, Dasheng Tian, Jun Qian, Guangrong Yu
Dioscin has been shown to play important roles in suppression of osteoclast maturation. It is proposed as a potential natural product for the treatment of osteoclast-related diseases. We hypothesized in this study that treatment of dioscin on bone marrow mesenchymal stem cells (BMSCs) could increase the osteo-chondrogenic differentiation of BMSCs and promote endochondral ossification of BMSCs in bone fracture environment. BMSCs were extracted from femur and tibia of male C57b mice. Stemness of BMSCs was studied by performing proliferation assay and multilineage differentiation...
2016: American Journal of Translational Research
Nanying Li, Juqing Song, Guanglin Zhu, Xiaoyu Li, Lei Liu, Xuetao Shi, Yingjun Wang
As always, the clinical therapy of critical size bone defects caused by trauma, tumor removal surgery or congenital malformation is facing great challenges. Currently, various approaches including autograft, allograft and cell-biomaterial composite based tissue-engineering strategies have been implemented to reconstruct injured bone. However, due to damage during the transplantation processes or design negligence of the bionic scaffolds, these methods expose vulnerabilities without the assistance of periosteum, a bilayer membrane on the outer surface of the bone...
October 18, 2016: Biomaterials Science
Jing-Guo Wu, Qing-Wei Jia, Yong Li, Fei-Fei Cao, Xi-Shan Zhang, Cong Liu
OBJECTIVE: This paper aimed to investigate ego modules for TGFβ3-induced chondrogenesis in mesenchymal stem cells (MSCs) using ego network algorithm. METHODS: The ego network algorithm comprised three parts, extracting differential expression network (DEN) based on gene expression data and protein-protein interaction (PPI) data; exploring ego genes by reweighting DEN; and searching ego modules by ego gene expansions. Subsequently, permutation test was carried out to evaluate the statistical significance of the ego modules...
September 28, 2016: Computational Biology and Chemistry
Aditya Arora, Anjaney Kothari, Dhirendra S Katti
: Matrix stiffness is known to play a pivotal role in cellular differentiation. Studies have shown that soft scaffolds (<2-3kPa) promote cellular aggregation and chondrogenesis, whereas, stiffer ones (>10kPa) show poor chondrogenesis in vitro. In this work we investigated if fibrin matrix from clotted blood can act as a soft surrogate which nullifies the influence of the underlying stiff scaffold, thus promoting chondrogenesis irrespective of bulk scale scaffold stiffness. For this we performed in vitro chondrogenesis on soft (∼1...
September 28, 2016: Acta Biomaterialia
F R Bhatti, A Mehmood, N Latief, S Zahra, H Cho, S N Khan, S Riazuddin
OBJECTIVE: Oxidative stress is a major obstacle against cartilage repair in osteoarthritis (OA). Anti-oxidant agents can play a vital role in addressing this issue. We evaluated the effect of Vitamin E preconditioning in improving the potential of mesenchymal stem cells (MSCs) to confer resistance against oxidative stress prevailing during OA. METHODS: Vitamin E pretreated MSCs were exposed to oxidative stress in vitro by hydrogen peroxide (H2O2) and also implanted in surgically-induced rat model of OA...
September 30, 2016: Osteoarthritis and Cartilage
G Portocarrero Huang, A Molina, N Tran, G Collins, T Livingston Arinzeh
Articular cartilage has a limited capacity to heal and currently, no treatment exists that can restore normal hyaline cartilage. Creating tissue engineering scaffolds that more closely mimic the native extracellular matrix may be an attractive approach. Glycosaminoglycans (GAGs), which are present in native cartilage tissue, provide signaling and structural cues to cells. This study evaluated the use of a GAG mimetic, derived from cellulose, as a potential scaffold for cartilage repair applications. Fully sulfated, sodium cellulose sulfate (NaCS) was initially evaluated in soluble form as an additive to cell culture media...
September 30, 2016: Journal of Tissue Engineering and Regenerative Medicine
Holly E Weiss-Bilka, Megan E McGann, Matthew J Meagher, Ryan K Roeder, Diane R Wagner
Key aspects of native endochondral bone development and fracture healing can be mimicked in mesenchymal stem cells (MSCs) through standard in vitro chondrogenic induction. Exploiting this phenomenon has recently emerged as an attractive technique to engineer bone tissue, however relatively little is known about the best conditions for doing so. The objective of this study was to compare the bone forming capacity and angiogenic induction of hypertrophic cell constructs containing human adipose-derived stem cells (hASCs) primed for chondrogenesis in two different culture systems: high-density pellets and alginate bead hydrogels...
September 30, 2016: Journal of Tissue Engineering and Regenerative Medicine
Margherita Tussellino, Raffaele Ronca, Rosa Carotenuto, Maria M Pallotta, Maria Furia, Teresa Capriglione
Chlorpyrifos (CPF) is an organophosphate insecticide used primarily to control foliage and soil-borne insect pests on a variety of food and feed crops. In mammals, maternal exposure to CPF has been reported to induce dose-related abnormalities such as slower brain growth and cerebral cortex thinning. In lower vertebrates, for example, fish and amphibians, teratogenic activity of this compound is correlated with several anatomical alterations. Little is known about the effects of CPF on mRNA expression of genes involved in early development of the anatomical structures appearing abnormal in embryos...
October 2016: Environmental and Molecular Mutagenesis
Makoto Hosoya, Sho Kanzaki, Satoko Wakabayashi, Kaoru Ogawa
Chondrodysplasia punctata (CP) is a systemic disorder of chondrogenesis. The most prominent features of patients with CP are abnormal faces characterized by a flat nose and short stature. CP patients show various types and levels of hearing loss. This disease is rare, and no successful tympanoplasties with hearing recovery have been reported. Here, we report on a CP case, in which hearing recovery was successfully treated with tympanoplasty.
September 22, 2016: Auris, Nasus, Larynx
R J Hinton, Y Jing, J Jing, J Q Feng
The formation of the mandibular condylar cartilage (MCC) and its subchondral bone is an important but understudied topic in dental research. The current concept regarding endochondral bone formation postulates that most hypertrophic chondrocytes undergo programmed cell death prior to bone formation. Under this paradigm, the MCC and its underlying bone are thought to result from 2 closely linked but separate processes: chondrogenesis and osteogenesis. However, recent investigations using cell lineage tracing techniques have demonstrated that many, perhaps the majority, of bone cells are derived via direct transformation from chondrocytes...
September 23, 2016: Journal of Dental Research
Weishen Chen, Lingwu Chen, Ziji Zhang, Fangang Meng, Guangxin Huang, Puyi Sheng, Zhiqi Zhang, Weiming Liao
Histone acetylation regulated by class I histone deacetylases (HDACs) plays a pivotal role in matrix-specific gene transcription and cartilage development. While we previously demonstrated that microRNA (miR)-455-3p is upregulated during chondrogenesis and can enhance early chondrogenesis, the mechanism underlying this process remains largely unclear. In this study, we characterized the effect of miR-455-3p on histone H3 acetylation and its role during cartilage development and degeneration. We observed that miR-455-3p was highly expressed in proliferating and pre-hypertrophic chondrocytes, while HDAC2 and HDAC8 were primarily expressed in hypertrophic chondrocytes...
September 13, 2016: Biochimica et Biophysica Acta
Zhiye Li, Ruikai Ba, Zhifa Wang, Jianhua Wei, Yimin Zhao, Wei Wu
: : Craniofacial deformities caused by congenital defects or trauma remain challenges for clinicians, whereas current surgical interventions present limited therapeutic outcomes. Injection of bone marrow-derived mesenchymal stem cells (BMSCs) into the defect is highly desirable because such a procedure is microinvasive and grafts are more flexible to fill the lesions. However, preventing hypertrophic transition and morphological contraction remain significant challenges. We have developed an "all host derived" cell transplantation system composed of chondrocyte brick (CB)-enriched platelet-rich plasma (P) gel and BMSCs (B)...
September 14, 2016: Stem Cells Translational Medicine
Federico Giuseppe Usuelli, Riccardo D'Ambrosi, Camilla Maccario, Michele Boga, Laura de Girolamo
PURPOSE: Autologous Matrix-Induced Chondrogenesis (AMIC(®)) is known to provide satisfactory clinical results for the treatment of knee, hip, and ankle cartilage lesions. The purpose of this study was to evaluate clinical and radiological outcomes of patients treated with a new all-arthroscopic AMIC(®) (AT-AMIC(®)) technique with autologous bone graft for talar osteochondral defects at a follow-up of 24 months. METHODS: Twenty patients underwent the AT-AMIC(®) procedure and autologous bone graft for type III and IV talar osteochondral lesions...
September 12, 2016: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
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