Rotator Cuff Tenocytes Differentiate into Hypertrophic Chondrocyte-Like Cells to Produce Calcium Deposits in an Alkaline Phosphatase-Dependent Manner

Darrieutort-Laffite, Christelle; Arnolfo, Paul; Garraud, Thomas; Adrait, Annie; Couté, Yohann; Louarn, G.; Trichet, Valérie; Layrolle, Pierre; Goff, Benoît Le; Blanchard, Frédéric

doi:10.3390/jcm8101544

Cited by 12 publications

(31 citation statements)

References 48 publications

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“…We first observed that synthetic apatite crystals used as control contained larger elements than patients' calcifications. After grinding, we obtained particles with size (1-100 µm length) and morphology (round shape) close to the human calcifications (Figure 1A) [3]. Therefore, we used the grinded synthetic crystals for the following experiments.…”

Section: Pro-inflammatory Effects Of Human Calcifications On Human Monocytes Macrophages and Tenocytesmentioning

confidence: 98%

“…Human crystals from calcific tendonitis were collected from symptomatic patients by ultrasound-guided needle lavage and stored in PBS (phosphate buffered saline) at -80°C as previously described [3]. All patients enrolled gave their formal consent.…”

Section: Crystal Preparationmentioning

confidence: 99%

“…Tenocyte-like cells were extracted from rotator cuff tendons as previously described [3]. They were plated in RPMI medium with 10% of FBS (5000 cells/well, 96-wellplate) and primed by LPS at 1µg/ml overnight then washed with PBS twice before crystal stimulation.…”

Section: Cellsmentioning

confidence: 99%

“…Calcific deposits appear between the tendon fibers after the formation of a fibrocartilaginous metaplasia containing chondrocyte-like cells [2]. These cells, derived from tenocytes, are able to mineralize the matrix through the action of alkaline phosphatase [3]. During the evolution of the disease, an acute inflammatory episode may occur leading to the disappearance of the calcification.…”

Section: Introductionmentioning

confidence: 99%

“…However, in all these data, authors used synthetic crystals and there is no data about the proinflammatory effects induced by carbonated apatite crystals extracted from patients suffering from calcific tendinopathy. Yet, human calcifications may differ from synthetic apatite through different particle size, shape and a rich protein content comprising most notably several proteins implicated in immune regulation such as Osteopontin [3,13]. It is not known if these…”

Section: Introductionmentioning

confidence: 99%

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Pro-inflammatory effects of human apatite crystals extracted from patients suffering from calcific tendinopathy.

Herman

Goff

Lima

et al. 2021

Preprint

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Background: Calcific tendonitis of the rotator cuff is due to carbonated apatite deposits in the shoulder tendons. During the evolution of the disease, an acute inflammatory episode may occur leading to the disappearance of the calcification. Although hydroxyapatite crystals-induced inflammation has been previously studied with synthetic crystals, no data are available with calcifications extracted from patients suffering from calcific tendinopathy. The objective of the study was to explore the inflammatory properties of human calcifications and the pathways involved. Methods: Human calcifications and synthetic hydroxyapatite were used in vitro to stimulate human monocytes and macrophages, the human myeloid cell line THP-1 and human tenocytes. The release of IL-1β, IL-6 and IL-8 by cells was quantified by ELISA. Gene expression of pro- and anti-inflammatory cytokines was evaluated by quantitative PCR. NF-kB activation and NLRP3 involvement was assessed in THP-1 cells using a NF-kB inhibitor and a Caspase 1 inhibitor. The inflammatory properties were then assessed in vivo using a mouse air pouch model. Results: Human calcifications were able to induce a significant release of IL-1β when incubated with monocytes, macrophages and THP-1 only if they were first primed with LPS (monocytes and macrophages) or PMA (THP-1). Stimulation of THP-1 by human calcifications led to similar levels of IL- 1β when compared to synthetic hydroxyapatite although these levels were significantly inferior in monocytes and macrophages. Patient’s crystals enhanced mRNA expression of pro-IL-1β, as well as IL-18, NF-kB and TGFβ when IL-6 and TNFα expression were not. IL-1β production was reduced by the inhibition of Caspase 1 indicating the role of NLRP3 inflammasome. In vivo, injection of human calcifications or synthetic hydroxyapatite in air pouch led to significant increase in membrane thickness although significant overexpression of IL-1β was only observed for synthetic hydroxyapatite. Conclusions: As synthetic hydroxyapatite, human calcifications were able to induce an inflammatory response resulting in the production of IL-1β after NF-kB activation and through NLRP3 inflammasome. In some experiments, IL-1β induction was lower with human calcifications compared to synthetic apatite. Differences in size, shape and protein content may explain this observation.

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Section: Pro-inflammatory Effects Of Human Calcifications On Human Monocytes Macrophages and Tenocytesmentioning

confidence: 98%

Section: Crystal Preparationmentioning

confidence: 99%

Section: Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pro-inflammatory effects of human apatite crystals extracted from patients suffering from calcific tendinopathy.

Herman

Goff

Lima

et al. 2021

Preprint

Self Cite

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Effect of hydroxyapatite content and particle size on the mechanical behaviors and osteogenesis in vitro of polyetheretherketone–hydroxyapatite composite

Wang

et al. 2021

Polymer Composites

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Poly-ether-ether-ketone (PEEK) possesses excellent biocompatibility and similar elastic modulus as bones but suffers from poor osseointegration; usually, the addition of hydroxyapatite (HA) is considered as an effective way to improve the osseointegration of PEEK implant interface. To investigate the effect of HA content and particle size on the mechanical behaviors and osteogenesis in vitro of PEEK-HA composites, the PEEK-HA specimens with variable HA content and particle size have been fabricated by powder mixing-heat press method and characterized by mechanical and biological tests. The results showed that the tensile/bending strength and elongation at break of PEEK-HA are significantly impaired as the increasing HA amount, but the modulus improves. The compressive strength and modulus are improved as the increasing amount of HA. The PEEK-HA with smaller HA particle size possesses higher-performance tensile/bending and lower-performance compressive properties. In osteogenesis tests in vitro, the results reveal that the cells amount attached on the substrate rises and the cells flatten more evenly with numerous cytoplasmic processes on greater area with the increasing HA content and decreasing particle size. The PEEK-HA group that HA content is 20 wt% and particle size is 20 nm exhibits optimal-performance osteogenesis in vitro, while maintaining sufficient mechanical properties.biological applications of polymers, composites, mechanical properties, thermoplastics | INTRODUCTIONPoly-ether-ether-ketone (PEEK) is linear aromatic semicrystalline thermoplastic engineering plastic; the macromolecular chain is composed of benzene ring connected by ether bond and ketone bond in counterpoint, and the outer electrons have a high delocalization range. [1] This structure makes it extremely stable and great resistant to chemicals, heat, and radiation. Such properties are extremely interesting for a large field of applications for high-end machinery manufacturing, nuclear engineering, aerospace, automotive industry, and orthopedic implants. [2][3][4][5][6] The research of PEEK-based biological composites has attracted extensive attention, since the biocompatibility of † These authors contributed equally to this work.

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Predicting the formation of different tissue types during Achilles tendon healing using mechanoregulated and oxygen-regulated frameworks

Notermans

Isaksson

2022

Biomech Model Mechanobiol

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During Achilles tendon healing in rodents, besides the expected tendon tissue, also cartilage-, bone- and fat-like tissue features have been observed during the first twenty weeks of healing. Several studies have hypothesized that mechanical loading may play a key role in the formation of different tissue types during healing. We recently developed a computational mechanobiological framework to predict tendon tissue production, organization and mechanical properties during tendon healing. In the current study, we aimed to explore possible mechanobiological related mechanisms underlying formation of other tissue types than tendon tissue during tendon healing. To achieve this, we further developed our recent framework to predict formation of different tissue types, based on mechanobiological models established in other fields, which have earlier not been applied to study tendon healing. We explored a wide range of biophysical stimuli, i.e., principal strain, hydrostatic stress, pore pressure, octahedral shear strain, fluid flow, angiogenesis and oxygen concentration, that may promote the formation of different tissue types. The numerical framework predicted spatiotemporal formation of tendon-, cartilage-, bone- and to a lesser degree fat-like tissue throughout the first twenty weeks of healing, similar to recent experimental reports. Specific features of experimental data were captured by different biophysical stimuli. Our modeling approach showed that mechanobiology may play a role in governing the formation of different tissue types that have been experimentally observed during tendon healing. This study provides a numerical tool that can contribute to a better understanding of tendon mechanobiology during healing. Developing these tools can ultimately lead to development of better rehabilitation regimens that stimulate tendon healing and prevent unwanted formation of cartilage-, fat- and bone-like tissues.

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Rotator Cuff Tenocytes Differentiate into Hypertrophic Chondrocyte-Like Cells to Produce Calcium Deposits in an Alkaline Phosphatase-Dependent Manner

Cited by 12 publications

References 48 publications

Pro-inflammatory effects of human apatite crystals extracted from patients suffering from calcific tendinopathy.

Pro-inflammatory effects of human apatite crystals extracted from patients suffering from calcific tendinopathy.

Effect of hydroxyapatite content and particle size on the mechanical behaviors and osteogenesis in vitro of polyetheretherketone–hydroxyapatite composite

Predicting the formation of different tissue types during Achilles tendon healing using mechanoregulated and oxygen-regulated frameworks

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