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Gary Gibson

Bio: Gary Gibson is an academic researcher from Henry Ford Hospital. The author has contributed to research in topics: Chondrocyte & Cartilage. The author has an hindex of 19, co-authored 38 publications receiving 1684 citations. Previous affiliations of Gary Gibson include Henry Ford Health System & University of California, Davis.

Papers
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Journal ArticleDOI
01 Feb 2001-Bone
TL;DR: It is suggested that collagen in bone is susceptible to the same NEG-mediated changes as collagen in other connective tissues and that an increased stiffness of the collagen network in bone due to NEG may explain some of the age-related increase in skeletal fragility and fracture risk.

476 citations

Journal ArticleDOI
01 Jul 2011-Gene
TL;DR: The findings suggest that miR-146a controls knee joint homeostasis and OA-associated algesia by balancing inflammatory responses in cartilage and synovium with pain-related factors in glial cells, and may be useful for the treatment of both cartilage regeneration and pain symptoms caused by OA.

167 citations

Journal ArticleDOI
Gary Gibson1
TL;DR: It is proposed that these changes produce effects that go far beyond the process of cell death and exert a focal influence on the endochondral ossification processes occurring in the microenvironment of the growth cartilage vascular interface.
Abstract: Endochondral ossification involves an ordered progression from cell division through hypertrophic differentiation to cell death. The apoptotic nature of chondrocyte death was first suggested by characteristic changes in morphology; and more recently by the pattern of DNA fragmentation and other characteristic features of apoptosis. In situ detection, although controversial, suggests that DNA fragmentation probably does not occur until late in hypertrophic differentiation. From observations of key features of apoptosis, including activation of the caspase cascade, changes in mitochondrial function, and expression of apoptosis inhibitors, the commitment of chondrocytes to apoptosis, appears to occur very early in hypertrophic differentiation. It is proposed that these changes produce effects that go far beyond the process of cell death and exert a focal influence on the endochondral ossification processes occurring in the microenvironment of the growth cartilage vascular interface. Endochondral ossification processes mediated by chondrocyte apoptosis may include intracellular calcium accumulation and release; matrix calcification; matrix resorption; maintenance of growth plate homeostasis; attraction of blood vessels and osteoblast precursors; and stimulation of bone formation.

160 citations

Journal ArticleDOI
TL;DR: It is concluded that terminal differentiation of chondrocytes results in death by an apoptotic process prior to resorption of the tissue and invasion by blood vessels.
Abstract: In the process of endochondral ossification, chondrocytes progress through a series of maturational changes, including division and hypertrophy, that culminate in chondrocyte loss and cartilage resorption. From an investigation of morphology, DNA fragmentation, and collagen synthesis in the developing chick sterna we have characterized chondrocytes death in this process. Light microscopy of resorbing sterna demonstrated chondrocyte condensation at the interface with the invading vasculature and electron microscopy demonstrated a range of chondrocyte morphologies, including retraction from the pericellular matrix, cytoplasmic and nuclear condensation, and vesiculation suggestive of sequential changes characteristic of apoptosis. Isolation and end-labeling of DNA from chick primary ossification centers demonstrated fragmentation to nucleosome sized units, only in primary ossification centers exhibiting active resorption, and in situ detection of DNA fragmentation showed a restriction to chondrocytes at the interface with invading blood. We conclude that terminal differentiation of chondrocytes results in death by an apoptotic process prior to resorption of the tissue and invasion by blood vessels. The extent of DNA fragmentation correlated closely with the proportion of cells displaying a condensed phenotype in contralateral primary ossification centers and peaked at an early stage of resorption, suggesting that chondrocyte apoptosis may be an initiating event in tissue resorption and vascular invasion. Comparison of DNA fragmentation with expression of the hypertrophic chondrocyte phenotype, as indicated by type X collagen synthesis, suggested that DNA fragmentation was a late event in the process of chondrocyte hypertrophy and probably corresponded with chondrocyte condensation. ©1995 Wiley-Liss, Inc.

132 citations

Journal ArticleDOI
TL;DR: Data indicated that type X collagen may play a role in ligament attachment to bone, originally thought to be associated with the cartilages undergoing endochondral bone formation.

90 citations


Cited by
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Journal ArticleDOI
TL;DR: This newer evidence suggests that AFFs are stress or insufficiency fractures, and studies with radiographic review consistently report significant associations between A FFs and BP use, although the strength and magnitude of effect vary.
Abstract: Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. © 2010 American Society for Bone and Mineral Research.

1,820 citations

Journal Article
TL;DR: In this article, Boudreau et al. proposed a method for suppressing ICE and apoptosis in Mammary Epithelial Cells by Extracellular Matrix (EMM).
Abstract: Suppression of ICE and Apoptosis in Mammary Epithelial Cells by Extracellular Matrix Nancy Boudreau,* Carolyn J. Sympson, Zena Werb, Mina J. Bissell N. Boudreau and M. J. Bissell Life Sciences Division, Lawrence Berkeley Laboratory 1 Cyclotron Road, Building 83, Berkeley, CA 94720, USA. C. J. Sympson Life Sciences Division, Lawrence Berkeley Laboratory 1 Cyclotron Road, Building 83, Berkeley, CA 94720, USA Laboratory of Radiobiology and Environmental Health University of California, San Francisco, CA 94143, USA. Z. Werb Laboratory of Radiobiology and Environmental Health University of California, San Francisco, CA 94143, USA. *To whom correspondence should be addressed. LBNL/DOE funding & contract number: DE-AC02-05CH11231 DISCLAIMER This document was prepared as an account of work sponsored by the United States Government. While this document is believed to contain correct information, neither the United States Government nor any agency thereof, nor The Regents of the University of California, nor any of their employees, makes any warranty, express or implied, or assumes any legal responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by its trade name, trademark, manufacturer, or otherwise, does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof, or The Regents of the University of California. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof or The Regents of the University of California.

1,139 citations

Journal ArticleDOI
TL;DR: This review focuses on the novel stress-induced and proinflammatory mechanisms underlying the pathogenesis of osteoarthritis, with particular attention to the role of synovitis and the contributions of other joint tissues to cellular events that lead to the onset and progression of the disease and irreversible cartilage damage.
Abstract: Purpose of review This review focuses on the novel stress-induced and proinflammatory mechanisms underlying the pathogenesis of osteoarthritis, with particular attention to the role of synovitis and the contributions of other joint tissues to cellular events that lead to the onset and progression of the disease and irreversible cartilage damage.

1,062 citations

Journal ArticleDOI
TL;DR: Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures.
Abstract: Introduction: Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a Task Force to address key questions related to this problem. Methods: A multi-disciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as pre-clinical studies that could provide insight into their pathogenesis. Results and Conclusions: A case definition was developed so that subsequent studies report on the same condition. The Task Force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their associations with cortical thickening, a periosteal reaction of the lateral cortex, a medial spike when the fracture is complete, prodromal pain, bilaterality, comorbid conditions and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end-products, mineralization, remodeling, vascularity and angiogenesis, lend biological plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared to the number of vertebral, hip and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure and there is concern that lack of awareness and under-reporting may mask the true incidence of the problem. Recommendations: Given the relative rarity of atypical femoral fractures, the Task Force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance and additional epidemiological and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopaedic and medical management.

1,024 citations

Journal ArticleDOI
TL;DR: The phenotype of the differentiated cell is defined and the sequential events leading from the undifferentiated stem cell to a mature chondrocyte are investigated by analysis of key matrix elements to understand in greater detail the sequential process of matrix assembly.

1,000 citations