Tendon-Specific Dicer Deficient Mice Exhibit Hypoplastic Tendon Through the Downregulation of Tendon-Related Genes and MicroRNAs

Omoto, Takenori; Yimiti, Dilimulati; Sanada, Yohei; Toriyama, Minoru; Ding, Chenyang; Hayashi, Yuta; Ikuta, Yasunari; Nakasa, Tomoyuki; Ishikawa, Masakazu; Sano, Masayuki; Lee, Minjung; Akimoto, Takayuki; Shukunami, Chisa; Miyaki, Shigeru; Adachi, Nobuo

doi:10.3389/fcell.2022.898428

Cited by 4 publications

(4 citation statements)

References 49 publications

(74 reference statements)

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“…In addition, the locomotor activity of SAMP8 was similar to that of SAMR1 at 20 weeks of age [ 31 ]. The relationship between OA severity and pain should be evaluated by combination of various new tools such as gait analysis based on motion capture system using marker less using AI technology [ 49 ], although it is difficult to evaluate pain in mouse OA model.…”

Section: Discussionmentioning

confidence: 99%

Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model

et al. 2022

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Background Animal models of spontaneous osteoarthritis (OA) are sparse and not well characterized. The purpose of the present study is to examine OA-related changes and mechanisms in senescence-accelerated mouse prone 8 (SAMP8) that displays a phenotype of accelerated aging. Methods Knees of male SAMP8 and SAM-resistant 1 (SAMR1) mice as control from 6 to 33 weeks of age were evaluated by histological grading systems for joint tissues (cartilage, meniscus, synovium, and subchondral bone), and µCT analysis. Gene expression patterns in articular cartilage were analyzed by real-time PCR. Immunohistochemistry was performed for OA-related factors, senescence markers, and apoptosis. Results Starting at 14 weeks of age, SAMP8 exhibited mild OA-like changes such as proteoglycan loss and cartilage fibrillation. From 18 to 33 weeks of age, SAMP8 progressed to partial or full-thickness defects with exposure of subchondral bone on the medial tibia and exhibited synovitis. Histological scoring indicated significantly more severe OA in SAMP8 compared with SAMR1 from 14 weeks [median (interquartile range): SAMR1: 0.89 (0.56–1.81) vs SAMP8: 1.78 (1.35–4.62)] to 33 weeks of age [SAMR1: 1.67 (1.61–1.04) vs SAMP8: 13.03 (12.26–13.57)]. Subchondral bone sclerosis in the medial tibia, bone mineral density (BMD) loss of femoral metaphysis, and meniscus degeneration occurred much earlier than the onset of cartilage degeneration in SAMP8 at 14 weeks of age. Conclusions SAMP8 are a spontaneous OA model that is useful for investigating the pathogenesis of primary OA and evaluating therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model

et al. 2022

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“…In human tendon constructs, COL1A1, COL6A3 and COL14A1 expression was detected on Day 0, increased until Day 7 and remained elevated and higher at Day 21 compared to Day 0 (Figure 4A-B). DPT (Dermatopontin) [59][60][61], DCN (Decorin) [62], POSTN (Periostin) [63] and THBS2 are involved in collagen fibrillogenesis and cell-matrix adhesion. Their mRNA expression was significantly increased during human tendon construct development (Figure 4C-D).…”

Section: Extracellular Matrix Gene Expression Was Correlated With Cha...mentioning

confidence: 99%

Human adipose stromal cells differentiate towards a tendon phenotype with extracellular matrix production and adapted visco-elastic properties in a 3D-culture system

Hordé,

Fouchard,

Laffray

et al. 2024

Preprint

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Tendons are composed of type I collagen fibrils and specialized extracellular matrix (ECM) proteins that are hierarchically organized to transmit forces from muscle to bone. Reliable and affordable models of human tendon constructs are requested to serve surgical treatment after tendon injury and in vitro pharmacological testing. Here, using human adipose stromal cells embedded in a 3D type-I collagen matrix and submitted to static uniaxial geometrical constraint, we generated human tendon constructs and assessed their mechanical properties and gene expression for up to 21 days in culture. The analysis of visco-elastic properties by nano-indentation indicated an increase in tissue stiffness (from about 1kPa at Day 0 to 10 kPa at Day 21), concomitant with a reduced percentage of stress relaxation, indicative of more solid-like mechanical properties. These changes in mechanical properties were associated with a reorganisation of ECM and the emergence of two cell populations, with one cell population organized as a ring in tissue periphery. In addition to the activation of the well-established tendon differentiation genetic program, assessed by the expression of SCX, MKX, TNMD and COL1A1, we validated the expression of a novel tendon marker, TM4SF1 and other components of the ECM such as COL6A3, COL14A1, DPT, DCN, POSTN and THBS2, which were previously identified in transcriptomic analyses of embryonic mouse limb tendons. In summary, this 3D culture system, which recapitulates most stages of tendon development, represent a potential route for human tendon regeneration. Key words: tendon constructs, visco-elastic properties, extra cellular matrix, human adipose stromal cells

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“…11 In mice, tendon/ligament-specific Dicer deletion induces an abnormal collagen fiber structure and downregulation of tendonrelated genes causing tendon dysplasia, indicating that Dicer has a role in tendon maturation in mice. 12 Phosphorylation of Dcr-1 increases postnatal mortality and accelerates aging and infertility in mice. 13 Suppression of Dcr-1 also significantly affects insect survival, development and reproduction.…”

Section: Introductionmentioning

confidence: 99%

“…In Caenorhabditis elegans , mutation of Dcr‐1 leads to oocyte abnormality and eggs failing to fertilize and hatch, which indicates the importance of Dcr‐1 in nematode reproduction 11 . In mice, tendon/ligament‐specific Dicer deletion induces an abnormal collagen fiber structure and downregulation of tendon‐related genes causing tendon dysplasia, indicating that Dicer has a role in tendon maturation in mice 12 . Phosphorylation of Dcr‐1 increases postnatal mortality and accelerates aging and infertility in mice 13 .…”

Section: Introductionmentioning

confidence: 99%

Functional characteristics of Dicer genes in Plutella xylostella

Huang,

Yu,

Asad

et al. 2024

Pest Management Science

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BACKGROUNDDicer is an endonuclease that belongs to the RNase III family and can specifically recognize and cleave double‐stranded RNA. In most insects, there are two Dicer genes, Dicer‐1 (Dcr‐1) and Dicer‐2 (Dcr‐2), which are involved in the microRNA (miRNA) and small‐interfering RNA (siRNA) pathways in many species, respectively. The function of Dicer in Plutella xylostella remains unknown.RESULTSThe full‐length open reading frame (ORF) of P. xylostella Dicer‐1 (PxDcr‐1) and Dicer‐2 (PxDcr‐2) were cloned and sequenced. Dcr‐1 and Dcr‐2 proteins shared similar structural domains with the Dicer‐partner binding domain (Dicer‐PBD) and the double‐strand RNA binding domain (dsRBD) only present in Dcr‐1. The phylogenetic trees showed that lepidopteran Dcr‐1s or Dcr‐2s clustered into one branch, with PxDcr‐1 in the basal position and PxDcr‐2 closest to Plodia interpunctella Dicer. Two homozygous knockout lines, ΔPxDcr‐1 and ΔPxDcr‐2, were obtained by using the CRISPR/Cas9 technique. The ΔPxDcr‐1 strain exhibited a high mortality rate, a low eclosion rate, a low egg‐laying rate, a low hatching rate, and a shriveled ovariole without mature eggs. The ΔPxDcr‐2 strain showed no significant difference from the wild‐type in terms of survival, development and reproduction, but the RNAi efficiency caused by dsRNA was significantly reduced.CONCLUSIONThese findings demonstrate the involvement of PxDcr‐1 in the development and reproduction of P. xylostella, specifically in the formation of ovarioles and eggs, and PxDcr‐2 is indispensable for RNAi. These findings shed light on the function of Dcr‐1 and Dcr‐2 in Lepidoptera.This article is protected by copyright. All rights reserved.

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Tendon-Specific Dicer Deficient Mice Exhibit Hypoplastic Tendon Through the Downregulation of Tendon-Related Genes and MicroRNAs

Cited by 4 publications

References 49 publications

Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model

Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model

Human adipose stromal cells differentiate towards a tendon phenotype with extracellular matrix production and adapted visco-elastic properties in a 3D-culture system

Functional characteristics of Dicer genes in Plutella xylostella

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