Effect of Angiogenesis-Related Cytokines on Rotator Cuff Disease: The Search for Sensitive Biomarkers of Early Tendon Degeneration

Savitskaya, Y.; Izaguirre, Aldo; Sierra, Luis; Pérez, Francisco Xavier Charlín; Cruz, Francisco; Villalobos, Enrique; Almazán, Arturo; Ibarra, Clemente

doi:10.4137/cmamd.s7071

Cited by 33 publications

(26 citation statements)

References 43 publications

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“…In addition, aberrant ECM production or fibrosis can potentially contribute to stiffness in the shoulder joint capsule which can lead to reductions in range of motion 65. Our findings support the body of evidence implicating the angiogenesis pathway in non-cancer musculoskeletal conditions such as tendon injuries or tendinopathy17,18 and rotator cuff disease (RCD) 19,20…”

Section: Discussionsupporting

confidence: 81%

<p>KDR inferred haplotype is associated with upper limb dysfunction in breast cancer survivors of mixed ancestry</p>

Mafu¹,

September²,

Shamley³

2019

CMAR

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Introduction: Shoulder pain and disability are well-documented sequelae of breast cancer treatment. Angiogenesis signaling may have a role in the development of shoulder pain or shoulder disability in breast cancer survivors. The aim of this study was to determine if polymorphisms in angiogenesis-related genes are associated with shoulder pain or disability following breast cancer treatment. Participants and methods: A cross-sectional study was conducted on 220 South African breast cancer survivors. The study aimed to evaluate associations between shoulder pain/disability and seven single nucleotide polymorphisms (SNPs) within five angiogenesis-associated genes: KDR (rs2305948 C>T; rs7667298 C>T), NOS3 (rs1549758 C>T), MMP2 (rs708269 A>T), THBS2 (rs9766678 A>G) and TIMP3 (rs5754312 T>A; rs715572 G>A). In addition, associations between shoulder pain/disability and inferred haplotypes for KDR and TIMP3 SNPs were evaluated. Participants were grouped into no–low and moderate–high shoulder pain/disability based on total pain/disability scores: ≤30 and >30, respectively using the shoulder pain and disability index (SPADI). Results: No independent associations with shoulder pain/disability categories were found for all SNPs. However, 1 inferred haplotype ( KDR “TT”) differed significantly ( P =0.014) between the shoulder disability categories. After adjusting for participants’ age, the differences in KDR inferred haplotype frequencies between shoulder disability categories became non-significant ( P =0.052). Conclusion: Our findings provide a preliminary suggestion of a possible association between polymorphisms in genes involved in angiogenesis and the presence of moderate–high shoulder disability among South African breast cancer survivors. A larger prospective cohort study is currently being conducted by our group.

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Section: Discussionsupporting

confidence: 81%

<p>KDR inferred haplotype is associated with upper limb dysfunction in breast cancer survivors of mixed ancestry</p>

Mafu¹,

September²,

Shamley³

2019

CMAR

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“…Tendon cells may therefore be partly responsible for the widespread angiogenesis which is known to occur in chronic tendinopathy [21].…”

Section: Discussionmentioning

confidence: 99%

Cyclic Strain Alters the Expression and Release of Angiogenic Factors by Human Tendon Cells

et al. 2014

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Angiogenesis is associated with the tissue changes underlying chronic overuse tendinopathy. We hypothesized that repetitive, cyclic loading of human tendon cells would lead to increased expression and activity of angiogenic factors. We subjected isolated human tendon cells to overuse tensile loading using an in vitro model (1 Hz, 10% equibiaxial strain). We found that mechanically stimulated human tendon cells released factors that promoted in vitro proliferation and tube formation by human umbilical vein endothelial cells (HUVEC). In response to cyclic strain, there was a transient increase in the expression of several angiogenic genes including ANGPTL4, FGF-2, COX-2, SPHK1, TGF-alpha, VEGF-A and VEGF-C, with no change in anti-angiogenic genes (BAI1, SERPINF1, THBS1 and 2, TIMP1-3). Cyclic strain also resulted in the extracellular release of ANGPTL4 protein by tendon cells. Our study is the first report demonstrating the induction of ANGPTL4 mRNA and release of ANGPTL4 protein in response to cyclic strain. Tenocytes may contribute to the upregulation of angiogenesis during the development of overuse tendinopathy.

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“…VEGF plays a role in tendinopathy. It is highly expressed in injured tendons, whereas its expression is almost completely downregulated in healthy tendons; in addition, VEGF stimulates the expression of MMPs and inhibits the expression of TIMPs (Savitskaya et al 2011).…”

Section: Discussionmentioning

confidence: 99%

In vitro tenocyte metabolism in aging and oestrogen deficiency

Torricelli

Veronesi

Pagani

et al. 2012

AGE

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Little is known about tendons and tenocyte biological behaviour during aging and, especially, oestrogen deficiency. The aim of this study was to evaluate in vitro the proliferation and metabolism of tenocytes isolated from the Achilles tendons of ovariectomised (OVX), middle-aged (OLD) and young (YOUNG) rats. An in vitro model of micro-wound healing was also used to assess age and oestrogen deficiency differences in tendon healing. In standard culture condition, OLD and OVX tenocytes showed a significantly lower proliferation rate, collagen I, aggrecan and elastin than YOUNG ones. In OVX group, fibronectin and elastin significantly decreased in comparison to YOUNG and OLD groups, respectively, whereas vascular endothelial growth factor and metalloproteinases-13 increased than those of both YOUNG and OLD groups. In the micro-wound healing model, tenocytes from both OVX and OLD showed a significantly lower healing rate, proliferation rate, collagen I and nitrix oxide in comparison to YOUNG. OVX elastin value was significantly lower than YOUNG one and OVX healing rate and cell migration speed, proliferation rate and fibronectin results were lower, whereas collagen III and metalloproteinase-13 higher in comparison to both YOUNG and OLD groups. These results highlighted how aging and, more significantly, oestrogen deficiency negatively affect tendon metabolism and healing. Our work improves the body of knowledge on the effects of senescence and oestrogen deficiency on tenocyte behaviour and allows further studies to find solution for the prevention of tendon injuries in aging and menopause.

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Effect of Angiogenesis-Related Cytokines on Rotator Cuff Disease: The Search for Sensitive Biomarkers of Early Tendon Degeneration

Cited by 33 publications

References 43 publications

<p>KDR inferred haplotype is associated with upper limb dysfunction in breast cancer survivors of mixed ancestry</p>

<p>KDR inferred haplotype is associated with upper limb dysfunction in breast cancer survivors of mixed ancestry</p>

Cyclic Strain Alters the Expression and Release of Angiogenic Factors by Human Tendon Cells

In vitro tenocyte metabolism in aging and oestrogen deficiency

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