Persistent Sox9 expression in hypertrophic chondrocytes suppresses transdifferentiation into osteoblasts

Lui, Julian C.; Yue, Shanna; Lee, Audrey; Kikani, Bijal; Temnycky, Adrian G.; Barnes, Kevin M.; Baron, Jeffrey

doi:10.1016/j.bone.2019.05.027

Cited by 41 publications

(45 citation statements)

References 24 publications

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“…In addition to facilitating chondrocyte differentiation, SOX9 also prevents osteoblast differentiation (19). Specifically, abnormal persistent Sox9 expression prevents transdifferentiation of terminal hypertrophic chondrocytes into osteoblasts (44); however, this does not directly address the contribution of BM mesenchymal stem cell-derived osteoblasts. The net effect of this imbalance between precocious chondrocyte differentiation and reduced osteoblast differentiation may lead to growth retardation in KS1, specifically to shortening of the long bones and decreased bone formation in Kmt2d +/βGeo mice.…”

Section: Discussionmentioning

confidence: 99%

Precocious chondrocyte differentiation disrupts skeletal growth in Kabuki syndrome mice

Fahrner¹,

Lin²,

Riddle³

et al. 2019

JCI Insight

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At time points where the variance of the random effect was estimated equal to 0, we fit a fixed-effects model using the genotype only. Finally, within each time point, we performed the post hoc pairwise comparisons among the 3 different genotypes using the emmeans R package, and we corrected for multiple testing using Tukey's adjustment method.Study approval. All experiments using laboratory mice were performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals

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Section: Discussionmentioning

confidence: 99%

Precocious chondrocyte differentiation disrupts skeletal growth in Kabuki syndrome mice

Fahrner¹,

Lin²,

Riddle³

et al. 2019

JCI Insight

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“…There are several possible mechanisms by which Sox9 might inhibit chondrocyte hypertrophy. Studies have shown that Sox9, as a major transcriptional activator, maintains the chondrocyte through a phosphoinositide 3-kinase (PI3K) -AKT pathway [44,45], as well as preventing chondrocytes from becoming hypertrophic [12]. In addition, Sox9 could block Wnt signaling through inducing the degradation of β-catenin to inhibit chondrogenic hypertrophy [46,47].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the differentiation of undifferentiated mesenchymal stem cells (MSCs) and polymerization of mesenchymal cells require the presence of Sox9 in the early stages of chondrogenesis. Chondrocyte and MSCs can develop into the body's skeleton during the late development of individuals, and Sox9 plays an important role in this process [12]. Therefore, we hypothesize that Sox9 is a candidate gene that could affect growth trait.…”

Section: Introductionmentioning

confidence: 96%

Detection of a 4 bp Mutation in the 3′UTR Region of Goat Sox9 Gene and Its Effect on the Growth Traits

Wang

et al. 2020

Animals

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The SRY-type HMG box 9 (Sox9) gene plays an important role in chondrocyte development as well as changes in hypertrophic chondrocytes, indicating that Sox9 can regulate growth in animals. However, no studies to date have examined the correlation between variations in Sox9 and growth traits in goats. Here, we found a 4 bp indel in the 3′UTR of Sox9 and verified its association with growth traits in Shaanbei white cashmere goats (n = 1109). The frequencies of two genotypes (ID and II) were 0.397 and 0.603, respectively, and polymorphic information content (PIC) values showed that the indel had a medium PIC (PIC > 0.25). The 4 bp indel was significantly correlated with body length (p = 0.006), heart girth (p = 0.001), and hip width (p = 4.37 × 10 −4). Notably, individuals with the ID genotype had significantly superior phenotypic traits compared with individuals bearing the II genotype. Hence, we speculated that the 4 bp indel is an important mutation affecting growth traits in goat, and may serve as an effective DNA molecular marker for marker-assisted selection in goat breeding programs.

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“…Those cells were mCherry + , identified by our Sox9-Tg line (solid arrowheads Fig 4B , 4C). Previous studies have correlated the downregulation of Sox9 in the HZ with the activation of the osteogenic program and the persistence of SOX9 with an inhibition of bone-related markers (Dy et al, 2012;Lui et al, 2019). The expression of OCN in HCs could point towards an early activation of an osteogenic program in those cells.…”

Section: Osteocalcin Is Expressed In Bone Cells and In Some Hypertrophic Chondrocytesmentioning

confidence: 95%

“…SOX9 is known to block osteoblast differentiation and to maintain columnar chondrocyte proliferation by delaying pre-hypertrophy, but also directing hypertrophic maturation (Dy et al, 2012;Hattori et al, 2010;Lui et al, 2019). The roles of SOX9 are various, and its expression in committed osteoblast has not been shown before, which suggests the presence of chondroosteogenic hybrid cells during the normal transition to the ossified skeleton in axolotl.…”

Section: Sox9 + /Ocn + Cellsmentioning

confidence: 99%

Post-embryonic development and aging of the appendicular skeleton inAmbystoma mexicanum

Riquelme-Guzmán

Schuez

Böhm

et al. 2021

Preprint

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Background: The axolotl is a key model organism for studying appendicular regeneration in vertebrates. The axolotl limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs develop post-embryonically. In this work, we evaluated the post-embryonic development of the appendicular skeleton and its changes with aging. Results: Juvenile skeletal elements are formed mostly by SOX9+/COL1A2+ cartilage cells. Ossification of the appendicular skeleton starts when animals reach a total length of 10 cm, and cartilage cells are replaced by a primary ossification center, consisting of cortical bone and an adipocyte-filled marrow cavity. Vascularization is associated to the ossification center and to the formation of the marrow cavity. We identified the contribution of Col1a2+ cells to bone and adipocytes. Moreover, ossification progresses with age towards the epiphyses of long bones. Even though axolotls are neotenic salamanders, ossification remains responsive to L-thyroxine, increasing the rate of bone formation. Conclusions: Bone maturation is a continuous process in axolotls that extends throughout the life span of the axolotls. Ossification of the appendicular bones is slow and continues until the complete element is ossified. The cellular components of the appendicular skeleton change accordingly during ossification, creating a heterogenous landscape in each element.

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Persistent Sox9 expression in hypertrophic chondrocytes suppresses transdifferentiation into osteoblasts

Cited by 41 publications

References 24 publications

Precocious chondrocyte differentiation disrupts skeletal growth in Kabuki syndrome mice

Precocious chondrocyte differentiation disrupts skeletal growth in Kabuki syndrome mice

Detection of a 4 bp Mutation in the 3′UTR Region of Goat Sox9 Gene and Its Effect on the Growth Traits

Post-embryonic development and aging of the appendicular skeleton inAmbystoma mexicanum

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