Regulation of hypoxia-induced cell death in human tenocytes

Liang, Min; Benson, Richard T.; Carr, Andrew; Hulley, P A

doi:10.1016/j.bone.2007.12.100

Cited by 5 publications

(9 citation statements)

References 29 publications

(40 reference statements)

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“…Nevertheless, a role for VEGF in sustaining protection and survival of tendon cells in line with the effects recently reported in human tenocytes (Liang et al. ) and chondrocytes (Maes et al. ) should not be excluded.…”

Section: Discussionmentioning

confidence: 93%

“…Healthy human tenocytes express several VEGF isoforms (Liang et al. ), and VEGFA mRNA is strongly upregulated following hypoxia under both low‐ and high‐serum conditions. Additionally, VEGF protein released in culture medium increased fourfold by anoxia, exercising a rescue role from cell death (Liang et al.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, VEGF protein released in culture medium increased fourfold by anoxia, exercising a rescue role from cell death (Liang et al. ).…”

Section: Discussionmentioning

confidence: 99%

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Cellular and molecular maturation in fetal and adult ovine calcaneal tendons

et al. 2014

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Processes of development during fetal life profoundly transform tendons from a plastic tissue into a highly differentiated structure, characterised by a very low ability to regenerate after injury in adulthood. Sheep tendon is frequently used as a translational model to investigate cell-based regenerative approaches. However, in contrast to other species, analytical and comparative baseline studies on the normal developmental maturation of sheep tendons from fetal through to adult life are not currently available. Thus, a detailed morphological and biochemical study was designed to characterise tissue maturation during mid- (2 months of pregnancy: 14 cm of length) and late fetal (4 months: 40 cm of length) life, through to adulthood. The results confirm that ovine tendon morphology undergoes profound transformations during this period. Endotenon was more developed in fetal tendons than in adult tissues, and its cell phenotype changed through tendon maturation. Indeed, groups of large rounded cells laying on smaller and more compacted ones expressing osteocalcin, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) were identified exclusively in fetal mid-stage tissues, and not in late fetal or adult tendons. VEGF, NGF as well as blood vessels and nerve fibers showed decreased expression during tendon development. Moreover, the endotenon of mid- and late fetuses contained identifiable cells that expressed several pluripotent stem cell markers [Telomerase Reverse Transcriptase (TERT), SRY Determining Region Y Box-2 (SOX2), Nanog Homeobox (NANOG) and Octamer Binding Transcription Factor-4A (OCT-4A)]. These cells were not identifiable in adult specimens. Ovine tendon development was also accompanied by morphological modifications to cell nuclei, and a progressive decrease in cellularity, proliferation index and expression of connexins 43 and 32. Tendon maturation was similarly characterised by modulation of several other gene expression profiles, including Collagen type I, Collagen type III, Scleraxis B, Tenomodulin, Trombospondin 4 and Osteocalcin. These gene profiles underwent a dramatic reduction in adult tissues. Transforming growth factor-1 expression (involved in collagen synthesis) underwent a similar decrease. In conclusion, these morphological studies carried out on sheep tendons at different stages of development and aging offer normal structural and molecular baseline data to allow accurate evaluation of data from subsequent interventional studies investigating tendon healing and regeneration in ovine experimental models.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Cellular and molecular maturation in fetal and adult ovine calcaneal tendons

et al. 2014

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“…VEGF is also demonstrated to have a role in sustaining the protection and survival of tendon cells [ 56 ]. Healthy human tenocytes express several VEGF isoforms [ 56 ], and VEGFA mRNA is strongly upregulated following hypoxia under both low- and high-serum conditions.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Innovation of Tendon Tissue Engineering Strategies

Citeroni

Ciardulli

Russo

et al. 2020

IJMS

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Tendinopathy is the term used to refer to tendon disorders. Spontaneous adult tendon healing results in scar tissue formation and fibrosis with suboptimal biomechanical properties, often resulting in poor and painful mobility. The biomechanical properties of the tissue are negatively affected. Adult tendons have a limited natural healing capacity, and often respond poorly to current treatments that frequently are focused on exercise, drug delivery, and surgical procedures. Therefore, it is of great importance to identify key molecular and cellular processes involved in the progression of tendinopathies to develop effective therapeutic strategies and drive the tissue toward regeneration. To treat tendon diseases and support tendon regeneration, cell-based therapy as well as tissue engineering approaches are considered options, though none can yet be considered conclusive in their reproduction of a safe and successful long-term solution for full microarchitecture and biomechanical tissue recovery. In vitro differentiation techniques are not yet fully validated. This review aims to compare different available tendon in vitro differentiation strategies to clarify the state of art regarding the differentiation process.

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“…Hypoxia symptoms have priority for degenerative tendons [14]. Hypoxia induced factor (HIF) is seen at rotator cuff ruptures [15]. A study consisting of 586 patients emphasizes that hypoxia linked to the nicotine-related vasoconstriction effect is a determiner for the occurrence and size of the rupture [16].…”

Section: Discussionmentioning

confidence: 99%