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Engineering Hypertrophic Chondrocyte-based Grafts for Enhanced Bone RegenerationBernhard, Jonathan C. January 2016 (has links)
Bone formation occurs through two ossification processes, intramembranous and endochondral. Intramembranous ossification is characterized by the direct differentiation of stem cells into osteoblasts, which then create bone. Endochondral ossification involves an intermediate step, as stem cells first differentiate into chondrocytes and produce a cartilage anlage. The chondrocytes mature into hypertrophic chondrocytes, which transform the cartilage anlage into bone. Bone tissue engineering has predominantly mimicked intramembranous ossification, creating osteoblast-based grafts through the direct differentiation of stem cells. Though successful in specific applications, greater adoption of osteoblast-based grafts has failed due to incomplete integration, limited regeneration, and poor mechanical maintenance. To overcome these obstacles, inspiration was drawn from native bone fracture repair, creating tissue engineered bone grafts replicating endochondral ossification.
Hypertrophic chondrocytes, the key cell in endochondral ossification, were differentiated from mesenchymal stem cell sources by first generating chondrocytes and then instigating maturation to hypertrophic chondrocytes. Conditions influencing this differentiation were investigated, indicating the necessity of prolonged chondrogenic cultivation and elevated oxygen concentrations to ensure widespread hypertrophic maturation. Comparing the bone production performance of differentiated hypertrophic chondrocytes to differentiated osteoblasts revealed that hypertrophic chondrocytes deposit significantly greater volume of bone mineral at a higher density than osteoblasts, albeit in a more juvenile form. When implanted subcutaneously, the hypertrophic chondrocytes stimulated turnover of this juvenile template into compact-like bone, whereas osteoblasts proceeded with processes similar to bone remodeling, generating spongy-like bone. Implanting these tissue engineered constructs into an orthotopic, critical-sized femoral defect saw hypertrophic chondrocyte-based constructs integrate quickly with the femur and facilitate the creation of significantly more bone, resulting in a successful bridging of the defect. The success of hypertrophic chondrocyte-based grafts in overcoming the failures of tissue engineered bone grafts demonstrates the potential of endochondral ossification inspired bone strategies and prompts its further investigation towards clinical utilization.
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ER-stress signaling and chondrocyte differentiation in miceLo, Ling-kit, Rebecca. January 2006 (has links)
Thesis (M. Phil.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.
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Evaluation of chitosan as a cell scaffolding material for cartilage tissue engineeringNettles, Dana Lynn, January 2001 (has links)
Thesis (M.S.)--Mississippi State University. Department of Agricultural and Biological Engineering. / Title from title screen. Includes bibliographical references.
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Genetic analyses of terminal differentiation of hypertrophic chondrocytesYang, Liu, January 2009 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves [202]-230). Also available in print.
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Genetic analyses of terminal differentiation of hypertrophic chondrocytes /Yang, Liu, January 2009 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves [202]-230). Also available online.
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The effect of fluid shear stress on growth plateDenison, Tracy Adam. January 2009 (has links)
Thesis (Ph.D)--Biomedical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Boyan, Barbara; Committee Co-Chair: Schwartz, Zvi; Committee Member: Bonewald, Lynda; Committee Member: Jo, Hanjoong; Committee Member: Sambanis, Athanassios. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Molecular control of osteo-chondroprogenitors formationLu, Luhui., 陆璐慧. January 2009 (has links)
published_or_final_version / Biochemistry / Master / Master of Philosophy
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Role(s) of p53/p63 in chondrocyte re-differentiation upon activation of ER stressPei, Lim-cho, Steven, 貝念祖 January 2012 (has links)
Endoplasmic Reticulum (ER) stress signal is a cellular response to various insults including
abnormal protein folding load, activating the unfolded protein response. Under severe ER stress,
apoptosis will occur in most cell types. Interestingly, this does not happen in a disease model for
Metaphyseal chondrodysplasia type Schmid (MCDS), where ER stress was activated in the
hypertrophic zone of the growth plate where mutant collagen X proteins that cannot be folded
correctly is expressed. Instead of normal progression from proliferating chondrocytes (PCs) to
hypertrophic chondrocytes (HCs) and conversion to bone, HCs in MCDS mice undergo
re-differentiation to PCs as a survival strategy due to an activation of ER stress. Transcription
factors are known to be important in regulating differentiation. p53 family members, as
transcription factors, are known to play important roles in developmental processes including
cellular reprogramming, thus, we hypothesize that the ectopic expression of key transcription
factors, p53 and TAp63, which are activated by ER stress is involved in HC re-differentiation. p53
is normally expressed in late PCs, Pre-HCs, and upper HCs, while TAp63 is expressed in PCs and
Pre-HCs suggesting they may have roles in chondrocyte differentiation. p53 activated under ER
stress in HCs are nuclear localized in MCDS mice, but did not invoke the apoptotic programme.
In this project, using quantitative analyse to study the expression level of p53 and p63 isoforms, it
was confirmed that p53 and TAp63γ are in part transcriptionally activated upon ER stress. From
functional study by inactivating p53 in MCDS mice, it was shown that p53 alone was not sufficient
to mediate re-differentiation. Given that TAp63γ isoforms is also highly upregulated upon ER
stress, and the negative regulator, ΔNp63, is downregulated, this combination of change in gene
expression also need to be considered.
Furthermore, known regulators of p53 and p63 activity such as ASPP1 and iASPP are also
differentially expressed in HCs, and are altered upon activation of ER stress favouring cell survival.
Thus, it would be important to evaluate the combination of TAp63 in the re-differentiation process
from conditional inactivation of p63 or in combination with p53 to gain a clearer understanding of
the contribution and relationship of these transcription factors in the survival strategy of stressed
HCs. / published_or_final_version / Biochemistry / Master / Master of Philosophy
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A study of some actions of growth-promoting peptides on skeletal cellsSoul, Jean H. January 1984 (has links)
No description available.
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Indian hedgehog stimulates chondrocyte hypertrophic differentiation in endochondral bone formationLi, Jun, January 2007 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.
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