Specific MicroRNAs Found in Extracellular Matrix Vesicles Regulate Proliferation and Differentiation in Growth Plate Chondrocytes

Asmussen, Niels C; Cohen, David J.; Zhao, Lin; McClure, Michael J.; Boyan, Barbara D.; Schwartz, Zvi

doi:10.1007/s00223-021-00855-y

Cited by 14 publications

(13 citation statements)

References 40 publications

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“…To validate our observations, in a second study we treated the rats with miR-122 mimic. We selected miR-122 for this analysis because it is also present in matrix vesicles produced by growth plate chondrocytes 4 , 8 and is elevated in OA rat articular cartilage 9 , but it reduces the effects of IL-1 β on production of MMP-13 or PGE2 in rat articular chondrocytes 9 . When 122-M injections were given on post-surgery days 3, 12 and 21 (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

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Prophylactic administration of miR-451 inhibitor decreases osteoarthritis severity in rats

Scott

Cohen

Kim

et al. 2022

Sci Rep

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Transfection of chondrocytes with microRNA-451(miR-451), present in growth zone cartilage of the growth plate, upregulates production of enzymes association with extracellular matrix degradation. miR-451 is also present in articular cartilage and exacerbates IL-1β effects in articular chondrocytes. Moreover, when osteoarthritis (OA) was induced in Sprague Dawley rats via bilateral anterior cruciate ligament transection (ACLT), miR-451 expression was increased in OA cartilage compared to control, suggesting its inhibition might be used to prevent or treat OA. To examine the prophylactic and therapeutic potential of inhibiting miR-451, we evaluated treatment with miR-451 power inhibitor (451-PI) at the onset of joint trauma and treatment after OA had developed. The prophylactic animal cohort received twice-weekly intra-articular injections of either 451-PI or a negative control (NC-PI) beginning on post-surgical day 3. OA was allowed to develop for 24 days in the therapeutic cohort before beginning injections. All rats were killed on day 45. Micro-CT, histomorphometrics, OARSI scoring, and muscle force testing were performed on samples. 451-PI mitigated OA progression compared to NC-PI limbs in the prophylactic cohort based on histomorphometric analysis and OARSI scoring, but no differences were detected by micro-CT. 451-PI treatment beginning 24 days post-surgery was not able to reduce OA severity. Prophylactic administration of 451-PI mitigates OA progression in a post-trauma ACLT rat model supporting its potential to prevent OA development following an ACLT injury clinically.

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Section: Resultsmentioning

confidence: 99%

“…miR-451a was specifically enriched 4 , 7 . When the growth plate chondrocytes were transfected with miR-451, production of enzymes associated with cartilage matrix degradation was increased 8 , suggesting it might also be involved in regulating the production and activity of these enzymes in articular cartilage.…”

Section: Introductionmentioning

confidence: 99%

Prophylactic administration of miR-451 inhibitor decreases osteoarthritis severity in rats

Scott

Cohen

Kim

et al. 2022

Sci Rep

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“…As dECM is degraded in tissue remodelling and repair, functional molecules are created through the breakdown of proteins as well as through the release of enzymes, growth factors, and other cell signalling molecules stored in the ECM in nanovesicles [ 23 , 58 ]. During degradation of the dECM, these proteins break down to release peptides that promote cell migration, proliferation, and remodelling, and play a role is modulating biological processes such as angiogenesis and the inflammatory response [ 23 , 26 , 27 , 28 , 29 , 59 , 60 ].…”

Section: Structure and Properties Of Ecmmentioning

confidence: 99%

Preparation and Use of Decellularized Extracellular Matrix for Tissue Engineering

McInnes

Möser

Chen

2022

JFB

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The multidisciplinary fields of tissue engineering and regenerative medicine have the potential to revolutionize the practise of medicine through the abilities to repair, regenerate, or replace tissues and organs with functional engineered constructs. To this end, tissue engineering combines scaffolding materials with cells and biologically active molecules into constructs with the appropriate structures and properties for tissue/organ regeneration, where scaffolding materials and biomolecules are the keys to mimic the native extracellular matrix (ECM). For this, one emerging way is to decellularize the native ECM into the materials suitable for, directly or in combination with other materials, creating functional constructs. Over the past decade, decellularized ECM (or dECM) has greatly facilitated the advance of tissue engineering and regenerative medicine, while being challenged in many ways. This article reviews the recent development of dECM for tissue engineering and regenerative medicine, with a focus on the preparation of dECM along with its influence on cell culture, the modification of dECM for use as a scaffolding material, and the novel techniques and emerging trends in processing dECM into functional constructs. We highlight the success of dECM and constructs in the in vitro, in vivo, and clinical applications and further identify the key issues and challenges involved, along with a discussion of future research directions.

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“… Anderson (1969 ) also indicated matrix vesicles of different sizes (estimated 300 A to estimated 1 micro) and shapes derived from cells that are identified in the epiphyseal cartilage matrix, which may contribute to the initiation of cartilage calcification. More specifically, matrix vesicles enriched with microRNAs may possess significant regulatory functions on growth plate chondrocytes ( Asmussen et al, 2021 ). Moreover, matrix vesicles presented with phospholipids also appear to be involved in the initial production of calcium HA crystals through the formation of phospholipid:Ca:Pi complexes ( Boyan et al, 1989 ).…”

Section: Physiological Roles Of CCLmentioning

confidence: 99%

Roles of the calcified cartilage layer and its tissue engineering reconstruction in osteoarthritis treatment

Wang

Xie

et al. 2022

Front. Bioeng. Biotechnol.

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Sandwiched between articular cartilage and subchondral bone, the calcified cartilage layer (CCL) takes on both biomechanical and biochemical functions in joint development and ordinary activities. The formation of CCL is not only unique in articular cartilage but can also be found in the chondro-osseous junction adjacent to the growth plate during adolescence. The formation of CCL is an active process under both cellular regulation and intercellular communication. Abnormal alterations of CCL can be indications of degenerative diseases including osteoarthritis. Owing to the limited self-repair capability of articular cartilage and core status of CCL in microenvironment maintenance, tissue engineering reconstruction of CCL in damaged cartilage can be of great significance. This review focuses on possible tissue engineering reconstruction methods targeting CCL for further OA treatment.

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Specific MicroRNAs Found in Extracellular Matrix Vesicles Regulate Proliferation and Differentiation in Growth Plate Chondrocytes

Cited by 14 publications

References 40 publications

Prophylactic administration of miR-451 inhibitor decreases osteoarthritis severity in rats

Prophylactic administration of miR-451 inhibitor decreases osteoarthritis severity in rats

Preparation and Use of Decellularized Extracellular Matrix for Tissue Engineering

Roles of the calcified cartilage layer and its tissue engineering reconstruction in osteoarthritis treatment

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