Changes in the integrins expression are related with the osteoarthritis severity in an experimental animal model in rats

Almonte-Becerril, Maylin; Costell, Mercedes; Kourí, Juan B.

doi:10.1002/jor.22649

Cited by 29 publications

(23 citation statements)

References 40 publications

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“…During the progression of OA, chondrocytes experience changes in integrin expression [45][46][47] . Since integrin α 5 β 1 binds not only regular fibronectin but also fibronectin fragments, depending on the ongoing physiological process, its activation can result in a detrimental physiological response 18,48 or a positive one, promoting cell survival 49 . Although there are reports of the upregulation of integrin α 5 β 1 in OA 46 , there is a lack of a detailed analysis of integrin clustering in chondrocytes in situ as a response to the progression of OA.…”

Section: Discussionmentioning

confidence: 99%

Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia

Hernández

Wells

Usheva

et al. 2020

Sci Rep

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Subjects with developmental dysplasia of the hip (DDH) often show early-onset osteoarthritis (oA); however, the molecular mechanisms underlying this pathology are not known. We investigated whether cellular changes in chondrocytes from oA cartilage can be detected in chondrocytes from DDH cartilage before histological manifestations of degeneration. We characterized undamaged and damaged articular cartilage from 22 participants having hip replacement surgery with and without DDH (9 DDH-OA, 12 OA-only, one femoral fracture). Tissue immunostaining revealed changes in damaged oA-only cartilage that was also found in undamaged DDH-oA cartilage. chondrocytes in situ from both groups show: (i) thicker fibers of vimentin intermediate filaments, (ii) clusters of integrin α 5 β 1 , (iii) positive MMP13 staining and (iv) a higher percentage of cells expressing the serine protease HtrA1. Further characterization of the extracellular matrix showed strong aggrecan and collagen II immunostaining in undamaged DDH cartilage, with no evidence of augmented cell death by activation of caspase 3. These findings suggest that early events in DDH cartilage originate at the chondrocyte level and that DDH cartilage may provide a novel opportunity to study these early changes for the development of therapeutic targets for oA. Although aging is among the various factors associated with the development of Osteoarthritis (OA) 1 , the incidence of OA has been increasing in younger populations. One study projected that the percentage of patients younger than 65 years old requiring total hip arthroplasty would increase from 41% in 2006 to 52% in 2030 2. These younger patients have a number of etiologies, including those with developmental dysplasia of the hip (DDH). In this condition, abnormal biomechanics leads to anomalous stress distribution within the hip joint and subsequent damage to the joint tissues including articular cartilage 3-6 and DDH is considered to be part of the congenital-biomechanical causes of OA 7. Chondrocytes, the cells of cartilage, are metabolically stimulated by different forms of mechanical loading including strain, shear, compression, tension, and hydrostatic loads, all of which are related to the structural and mechanical integrity of the joint. At the tissue-level, the extracellular matrix (ECM) 8 , composed mostly of collagen II and proteoglycans, gives mechanical integrity, while at the cellular-level the cytoskeleton fulfills this role, with vimentin intermediate filaments playing a major function 9,10. Mechanical load, in turn, regulates both cytoskeleton dynamics 11,12 and the synthesis of key ECM proteins 13,14. Of the key ECM components regulating mechanical signals to chondrocytes, fibronectin mediates pathways associated with cell growth and survival, for example promoting chondrocyte survival via integrin α 5 β 1 binding 15. However, in contrast, fibronectin fragments, produced via cleavage by proteases such as the High-Temperature Requirement protein A1 (HtrA1) 16 , activate catabolic pathways 17,18. In...

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Section: Discussionmentioning

confidence: 99%

Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia

Hernández

Wells

Usheva

et al. 2020

Sci Rep

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“…Chondrocytes express various subunits of integrin- and integrin- (2). Furthermore, the profile of integrin expression is dynamically regulated during chondrogenic differentiation (3,4) and development of disease, such as osteoarthritis (OA) (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

ITGBL1 modulates integrin activity to promote cartilage formation and protect against arthritis

et al. 2018

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Developing and mature chondrocytes constantly interact with and remodel the surrounding extracellular matrix (ECM). Recent research indicates that integrin-ECM interaction is differentially regulated during cartilage formation (chondrogenesis). Integrin signaling is also a key source of the catabolic reactions responsible for joint destruction in both rheumatoid arthritis and osteoarthritis. However, we do not understand how chondrocytes dynamically regulate integrin signaling in such an ECM-rich environment. Here, we found that developing chondrocytes express integrin-β–like 1 (Itgbl1) at specific stages, inhibiting integrin signaling and promoting chondrogenesis. Unlike cytosolic integrin inhibitors, ITGBL1 is secreted and physically interacts with integrins to down-regulate activity. We observed that Itgbl1 expression was strongly reduced in the damaged articular cartilage of patients with osteoarthritis (OA). Ectopic expression of Itgbl1 protected joint cartilage against OA development in the destabilization of the medial meniscus–induced OA mouse model. Our results reveal ITGBL1 signaling as an underlying mechanism of protection against destructive cartilage disorders and suggest the potential therapeutic utility of targeting ITGBL1 to modulate integrin signaling in human disease.

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“…Fixed samples were cryosectioned (Leica CM 1100; Heerbrugg, Switzerland) and mounted on gelatin coated slides. Tissues were processed for IF as has been described elsewhere [28]. In order to identify type I Collagen, type II Collagen and MMP13 in chondrocytes, independent samples were incubated with rabbit (Abcam pcl, CA, UK).…”

Section: Immunofluorescencementioning

confidence: 99%

“…As secondary antibody FITC-tagged donkey anti-rabbit (Jackson Immuno Research Laboratories, Inc, WestGrove) was used. Then, all samples were observed through a Leica confocal microscope (TCS-SP5-DMI6000B with Plan Neor Fluor at 63X objective) [10,28].…”

Section: Immunofluorescencementioning

confidence: 99%