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Chondrocyte motility

Rachel N Frisch, Kevin M Curtis, Kristina K Aenlle, Guy A Howard
INTRODUCTION: Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into multiple cell types, including osteoblasts, chondrocytes, and adipocytes. These pluripotent cells secrete hepatocyte growth factor (HGF), which regulates cell growth, survival, motility, migration, mitogenesis and is important for tissue development/regeneration. HGF has four splice variants, NK1, NK2, NK3, and NK4 which have varying functions and affinities for the HGF receptor, cMET. HGF promotes osteoblastic differentiation of MSCs into bone forming cells, playing a role in bone development, health and repair...
September 2016: Expert Opinion on Therapeutic Targets
Hyunjun Shin, Mi Nam Lee, Jin Seung Choung, Sanghee Kim, Byung Hyune Choi, Minsoo Noh, Jennifer H Shin
The expansion of autologous chondrocytes in vitro is used to generate sufficient populations for cell-based therapies. However, during monolayer culture, chondrocytes lose inherent characteristics and shift to fibroblast-like cells as passage number increase. Here, we investigated passage-dependent changes in cellular physiology, including cellular morphology, motility, and gene and protein expression, as well as the role of focal adhesion and cytoskeletal regulation in the dedifferentiation process. We found that the gene and protein expression levels of both the focal adhesion complex and small Rho GTPases are upregulated with increasing passage number and are closely linked to chondrocyte dedifferentiation...
August 2016: Journal of Cellular Physiology
Frank Y Zhou, Ai-Qun Wei, Bojiang Shen, Lisa Williams, Ashish D Diwan
BACKGROUND: Intervertebral disc degeneration is a major cause of low back pain. Previous researches have demonstrated local administration of signalling molecules as potential biological therapies for disc regeneration. Our laboratory has published encouraging results for effectiveness of injection of the cartilage derived morphogenetic protein-2 (CDMP-2) into ovine discs following annular injury. To elucidate the mechanisms underpinning these in vivo effects, this project aimed to investigate the potential of CDMP-2 on cellular migration, proliferation and extracellular matrix production in a human chondrocytic cell line...
2015: International Journal of Spine Surgery
Yun Hyun Huh, Gyuseok Lee, Keun-Bae Lee, Jeong-Tae Koh, Jang-Soo Chun, Je-Hwang Ryu
INTRODUCTION: Pannus formation and resulting cartilage destruction during rheumatoid arthritis (RA) depends on the migration of synoviocytes to cartilage tissue. Here, we focused on the role of hypoxia-inducible factor (HIF)-2α-induced chemokines by chondrocytes in the regulation of fibroblast-like synoviocyte (FLS) migration into the cartilage-pannus interface and cartilage erosion. METHODS: Collagen-induced arthritis (CIA), K/BxN serum transfer, and tumor necrosis factor-α transgenic mice were used as experimental RA models...
2015: Arthritis Research & Therapy
Kang Tian, Weiliang Zhong, Xifu Zheng, Jinrui Zhang, Pixu Liu, Weiguo Zhang, Han Liu
Cartilage defect is an intractable clinical problem. Therapeutic strategies for cartilage repair are far from optimal due to poor proliferation capacity of chondrocytes. Autologous chondrocyte implantation is a cell based therapy that uses in vitro amplified healthy chondrocytes from the patient. However, chondrocyte dedifferentiation during in vitro culture limits its application. Neuroleukin (NLK) is a multifunctional protein that stimulates cell growth and migration, together with its receptor autocrine motility factor receptor (AMFR, also called gp78)...
2015: Scientific Reports
Florentine C Moazedi-Fuerst, Gerald Gruber, Martin H Stradner, Diego Guidolin, Jonathan C Jones, Koppany Bodo, Karin Wagner, Daniela Peischler, Verena Krischan, Jennifer Weber, Patrick Sadoghi, Mathias Glehr, Andreas Leithner, Winfried B Graninger
Formation of chondrocyte clusters is not only a morphological sign of osteoarthritis but it is also observed in cell culture. Active locomotion of chondrocytes is controlled by integrins in vitro. Integrins bind to Laminin-A4 (LAMA4), a protein that is highly expressed in vivo in clusters of hypertrophic chondrocytes. We tested if LAMA4 is relevant for cluster formation. Human chondrocytes were cultured in a 2D matrigel model and treated with different concentrations of a monoclonal inhibitory anti-LAMA4-antibody...
March 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Niina Hopper, Frances Henson, Roger Brooks, Erden Ali, Neil Rushton, John Wardale
INTRODUCTION: A major problem in cartilage repair is the lack of chondrogenic cells migrating from healthy tissue into defects. Cartilage is essentially avascular and therefore its healing is not considered to involve mononuclear cells. Peripheral blood derived mononuclear cells (PBMC) offer a readily available autologous cell source for clinical use and therefore this study was designed to evaluate the effects of PBMCs on chondrocytes and cartilage. METHODS: Human primary chondrocytes and cartilage tissue explants were taken from patients undergoing total knee replacement (n = 17)...
2015: Arthritis Research & Therapy
Liru Li, Dejun Wang, Jun Zhou, Yan Cheng, Tian Liang, Guangmei Zhang
The mesenchymal stem cells (MSCs) derived from amniotic fluid (AF) have become an attractive stem cells source for cell-based therapy because they can be harvested at low cost and avoid ethical disputes. In human research, stem cells derived from AF gradually became a hot research direction for disease treatment, specifically for their plasticity, their reduced immunogenicity and their tumor tropism regardless of the tumor size, location and source. Our work aimed to obtain and characterize human amniotic fluid mesenchymal stem cells (AFMSCs) and detect their ovarian cancer tropsim in nude mice model...
2015: PloS One
A R Tan, E Alegre-Aguarón, G D O'Connell, C D VandenBerg, R K Aaron, G Vunjak-Novakovic, J Chloe Bulinski, G A Ateshian, C T Hung
OBJECTIVE: Galvanotaxis, the migratory response of cells in response to electrical stimulation, has been implicated in development and wound healing. The use of mesenchymal stem cells (MSCs) from the synovium (synovium-derived stem cells, SDSCs) has been investigated for repair strategies. Expansion of SDSCs is necessary to achieve clinically relevant cell numbers; however, the effects of culture passage on their subsequent cartilaginous extracellular matrix production are not well understood...
February 2015: Osteoarthritis and Cartilage
G Aaron Hobbs, Lauren E Mitchell, Megan E Arrington, Harsha P Gunawardena, Molly J DeCristo, Richard F Loeser, Xian Chen, Adrienne D Cox, Sharon L Campbell
The Rac1 GTPase is an essential and ubiquitous protein that signals through numerous pathways to control critical cellular processes, including cell growth, morphology, and motility. Rac1 deletion is embryonic lethal, and its dysregulation or mutation can promote cancer, arthritis, cardiovascular disease, and neurological disorders. Rac1 activity is highly regulated by modulatory proteins and posttranslational modifications. Whereas much attention has been devoted to guanine nucleotide exchange factors that act on Rac1 to promote GTP loading and Rac1 activation, cellular oxidants may also regulate Rac1 activation by promoting guanine nucleotide exchange...
February 2015: Free Radical Biology & Medicine
R Ruhlen, K Marberry
UNLABELLED: The presence and role of primary, or non-motile, cilia on chondrocytes has confused cartilage researchers for decades. Initial explanations attributed a vestigial nature to chondrocyte cilia. Evidence is now emerging that supports the role of the chondrocyte primary cilium as a sensory organelle, in particular, in mechanotransduction and as a compartment for signaling pathways. Early electron microscopy images depicted bent cilia aligned with the extracellular matrix (ECM) in a manner that suggested a response to mechanical forces...
August 2014: Osteoarthritis and Cartilage
Ganna Aleshcheva, Jayashree Sahana, Xiao Ma, Jens Hauslage, Ruth Hemmersbach, Marcel Egli, Manfred Infanger, Johann Bauer, Daniela Grimm
Tissue engineering of chondrocytes on a Random Positioning Machine (RPM) is a new strategy for cartilage regeneration. Using a three-dimensional RPM, a device designed to simulate microgravity on Earth, we investigated the early effects of RPM exposure on human chondrocytes of six different donors after 30 min, 2 h, 4 h, 16 h, and 24 h and compared the results with the corresponding static controls cultured under normal gravity conditions. As little as 30 min of RPM exposure resulted in increased expression of several genes responsible for cell motility, structure and integrity (beta-actin); control of cell growth, cell proliferation, cell differentiation and apoptosis (TGF-β1, osteopontin); and cytoskeletal components such as microtubules (beta-tubulin) and intermediate filaments (vimentin)...
2013: PloS One
Kai Lee Yap, Polina Sysa-Shah, Brad Bolon, Ren-Chin Wu, Min Gao, Alice L Herlinger, Fengying Wang, Francesco Faiola, David Huso, Kathleen Gabrielson, Tian-Li Wang, Jianlong Wang, Ie-Ming Shih
NAC1 encoded by NACC1 is a member of the BTB/POZ family of proteins and participates in several pathobiological processes. However, its function during tissue development has not been elucidated. In this study, we compared homozygous null mutant Nacc1(-/-) and wild type Nacc1(+/+) mice to determine the consequences of diminished NAC1 expression. The most remarkable change in Nacc1(-/-) mice was a vertebral patterning defect in which most knockout animals exhibited a morphological transformation of the sixth lumbar vertebra (L6) into a sacral identity; thus, the total number of pre-sacral vertebrae was decreased by one (to 25) in Nacc1(-/-) mice...
2013: PloS One
Chih-Yang Lin, Sunny Li-Yun Chang, Yi-Chin Fong, Chin-Jung Hsu, Chih-Hsin Tang
Chondrosarcoma is the primary malignancy of bone that is characterized by a potent capacity to invade locally and cause distant metastasis, and is therefore associated with poor prognoses. Chondrosarcoma further shows a predilection for metastasis to the lungs. The brain-derived neurotrophic factor (BDNF) is a small molecule in the neurotrophin family of growth factors that is associated with the disease status and outcome of cancers. However, the effect of BDNF on cell motility in human chondrosarcoma cells is mostly unknown...
2013: International Journal of Molecular Sciences
Chih-Yang Lin, Hui-Jye Chen, Te-Mao Li, Yi-Chin Fong, Shan-Chi Liu, Po-Chun Chen, Chih-Hsin Tang
Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis; it has a poor prognosis and shows a predilection for metastasis to the lungs. Brain derived neurotrophic factor (BDNF) is a small-molecule protein from the neurotrophin family of growth factors that is associated with the disease status and outcomes of cancers. However, the effect of BDNF on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma tissues showed significant expression of BDNF, which was higher than that in normal cartilage and primary chondrocytes...
2013: PloS One
Yongxing Cao, Xin Zhang, Wei Shang, Jiejia Xu, Xianhua Wang, Xiaoqing Hu, Yingfang Ao, Heping Cheng
OBJECTIVE: Mitochondria play important roles in many types of cells. However, little is known about mitochondrial function in chondrocytes. This study was undertaken to explore possible role of mitochondrial oxidative stress in inflammatory response in articular chondrocytes. METHODS: Chondrocytes and cartilage explants were isolated from wild type or transgenic mice expressing the mitochondrial superoxide biosensor - circularly permuted yellow fluorescent protein (cpYFP)...
2013: PloS One
Edward H Schuchman, Yi Ge, Alon Lai, Yury Borisov, Meghan Faillace, Efrat Eliyahu, Xingxuan He, James Iatridis, Helen Vlassara, Gary Striker, Calogera M Simonaro
BACKGROUND: Pentosan polysulfate (PPS) is an FDA-approved, oral medication with anti-inflammatory and pro-chondrogenic properties. We have previously shown that animal models of the mucopolysaccharidoses (MPS) exhibit significant inflammatory disease, contributing to cartilage degeneration. Enzyme replacement therapy (ERT) only partly reduced inflammation, and anti-TNF-alpha antibody therapy significantly enhanced clinical and pathological outcomes. Here we describe the use of PPS for the treatment of MPS type VI rats...
2013: PloS One
L D Wright, K D McKeon-Fischer, Z Cui, L S Nair, J W Freeman
Osteoarthritis (OA) is the most prevalent musculoskeletal disease in humans, causing pain, loss of joint motility and function, and severely reducing the standard of living of patients. Cartilage tissue engineering attempts to repair the damaged tissue of individuals suffering from OA by providing mechanical support to the joint as new tissue regenerates. The aim of this study was to create composite three dimensional scaffolds comprised of electrospun poly(D,L-lactide)/poly(L-lactide) (PDLA/PLLA) or poly(D,L-lactide)/polycaprolactone (PDLA/PCL) with salt leached pores and an embedded chitosan hydrogel to determine the potential of these scaffolds for cartilage tissue engineering...
December 2014: Journal of Tissue Engineering and Regenerative Medicine
Abigail Cline, Ningguo Gao, Heather Flanagan-Steet, Vandana Sharma, Sabrina Rosa, Roberto Sonon, Parastoo Azadi, Kirsten C Sadler, Hudson H Freeze, Mark A Lehrman, Richard Steet
Congenital disorder of glycosylation (PMM2-CDG) results from mutations in pmm2, which encodes the phosphomannomutase (Pmm) that converts mannose-6-phosphate (M6P) to mannose-1-phosphate (M1P). Patients have wide-spectrum clinical abnormalities associated with impaired protein N-glycosylation. Although it has been widely proposed that Pmm2 deficiency depletes M1P, a precursor of GDP-mannose, and consequently suppresses lipid-linked oligosaccharide (LLO) levels needed for N-glycosylation, these deficiencies have not been demonstrated in patients or any animal model...
November 2012: Molecular Biology of the Cell
Chih-Yuan Chen, Kuan-Chih Hsiau, C A Chung
The Boyden chamber assay measures the coefficients of cell motility by fitting the experiments with theoretical calculations. Under the circumstance of rapid receptor kinetics, the distribution of chemical-receptor complexes on the cell surface can be treated as being quasi-steady and chemotaxis is directly related to the biochemical concentration, leading to the celebrated Keller-Segel model, which has been shown to be an approximation to the full receptor-mediated form. No matter approximate or full, these approaches have ignored cell sedimentation in the upper chamber, assuming that all the cells have already resided on the filter top at the beginning of the test...
September 2013: Mathematical Medicine and Biology: a Journal of the IMA
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