Biology subjects

Joeng, K. S.

Publications and source records attributed to Joeng, K. S..

4 recordsLinked to original sources

bioRxiv2024

mTORC1 and STAT3 signalings are indispensable for in vitro TGFβ1-dependent Three-Dimensional (3D) tendon construct.

The Transforming Growth Factor-{beta} 1 (TGF{beta}1) is a well-known growth factor involved in tenocytes differentiation, extracellular matrix production, and cell fate regulation. We previously demonstrated that TGF{beta}1 has a critical role in the formation of in vitro 3D tendon constructs using mouse primary tendon cells. In this study, we investigated the function of Mammalian target of rapamycin complex 1 (mTORC1) and Signal transducer and activator of transcription 3 (STAT3) signaling in the formation of TGF{beta}1-induced in vitro 3D tendon constructs using specific inhibitors, rapamycin (mTORC1 inhibitor) and stattic (stat3 inhibitor). TGF{beta}1 treatment activated both mTORC1 and STAT3 in 3D tendon constructs. The treatment of rapamycin or stattic partly attenuated TGF{beta}1-dependent cellular, molecular, and matrix changes in the 3D tendon constructs. Overall, this study demonstrates that mTORC1-STAT3 signaling axis is a downstream mediator of TGF{beta}1 signaling in the formation of 3D tendon constructs.

bioengineering↗

bioRxiv2022

Tendon-like cellular and matrix maturation in scaffold-free three-dimensional tendon cell culture using mouse tendon cells

Tendons transmit mechanical forces between muscle and bone. Their biomechanical function requires high tensile strength provided by highly organized collagen fibers. Tenocytes mainly drive tendon growth via extracellular matrix (ECM) production and organization. The biological mechanisms regulating tenocyte differentiation and morphological maturation have not been well-established, partly due to the lack of reliable in vitro systems that produce highly aligned collagenous tissues. In this study, we developed a scaffold-free, three-dimensional (3D) tendon culture system using mouse tendon cells and a differentially adherent growth channel. TGF{beta} treatment promoted tendon-like structure in the peripheral layer of the constructs with decreased cell density, decreased cell proliferation, increased thickness, and more elongated cells within highly aligned extracellular matrix. The constructs were used to understand the function of TGF{beta} signaling in tenogenic differentiation, collagen fibrillogenesis, and biomechanical properties. This scaffold-free 3D constructs system can serve as a reliable in vitro system to study underlying biological mechanisms that regulate cellular and matrix maturation in tendon development and growth.

bioengineering↗

bioRxiv2020

Rcn3 is Involved in Postnatal Tendon Development by Regulating Collagen Modification and Fibrillogenesis

Tendon plays a critical role in the joint movement by transmitting force from muscle to bone. This transmission of force is facilitated by its specialized structure, which consists of highly aligned extracellular matrix consisting predominantly of type I collagen. Tenocytes, fibroblast-like tendon cells residing between the parallel collagen fibers, regulate this specialized tendon matrix. Despite the importance of collagen structure and tenocyte function, the biological mechanisms regulating fibrillogenesis and tenocyte maturation are not well understood. Here we examine the function of Reticulocalbin 3 (Rcn3) in collagen fibrillogenesis and tenocyte maturation during postnatal tendon development using a genetic mouse model. Loss of Rcn3 in tendon caused decreased tendon thickness, abnormal tendon cell maturation, and decreased mechanical properties. Interestingly, Rcn3 deficient mice exhibited a smaller collagen fibril distribution and over-hydroxylation in C-telopeptide cross-linking lysine from 1(1) chain. Additionally, the proline 3-hydroxylation sites in type I collagen were also over-hydroxylated in Rcn3 deficient mice. Our data collectively suggest that Rcn3 is a pivotal regulator of collagen fibrillogenesis and tenocyte maturation during postnatal tendon development.

developmental biology↗

bioRxiv2020

COPB2 haploinsufficiency causes a coatopathy with osteoporosis and developmental delay

Coatomer complexes function in the sorting and trafficking of proteins between subcellular organelles. Pathogenic variants in coatomer subunits or associated factors have been reported in multi-systemic disorders, i.e., coatopathies, that can affect the skeletal and central nervous systems. We have identified loss-of-function variants in COPB2, a component of the coatomer complex I (COPI), in individuals presenting with osteoporosis, fractures and developmental delay of variable severity. Because the role of COPB2 in bone has not been characterized, we studied the effect of COPB2 deficiency on skeletal development in mice and zebrafish. Copb2+/- mice showed low bone mass and decreased bone strength. In zebrafish, larvae carrying a copb2 heterozygous frameshift variant showed delayed mineralization. copb2-null embryos showed endoplasmic reticulum (ER) and Golgi disorganization, and embryonic lethality. COPB2 siRNA-treated fibroblasts showed delayed collagen trafficking with retention of type I collagen in the ER and Golgi, and altered distribution of Golgi markers. Our data suggest that COPB2 haploinsufficiency leads to disruption of intracellular collagen trafficking and osteoporosis, which may improve with ascorbic acid supplementation. This work highlights the role of COPI complex as a critical regulator of bone mass and identifies a new form of coatopathy due to COPB2 deficiency.

genetics↗