Worldwide, calcific aortic valve disease is one of the leading causes of morbidity and mortality among patients with cardiac abnormalities. Aortic valve mineralization and calcification are the key events of adult calcific aortic valve disease manifestation and functional insufficiency. Due to heavy mineralization and calcification, adult aortic valvular cusps show disorganized and dispersed stratification concomitant with deposition of calcific nodules with severely compromised adult valve function. Interestingly, shared gene regulatory pathways are identified between bone-forming cells and heart valve cells during development. Asporin, a small leucine-rich proteoglycan (43&#x2009;kDa), acts to inhibit mineralization in periodontal ligament cells and is also detected in normal murine adult aortic valve leaflets with unknown function. Therefore, to understand the Asporin function in aortic cusp mineralization and calcification, adult avian aortic valvular interstitial cell culture system is established and osteogenesis has been induced in these cells successfully. Upon induction of osteogenesis, reduced expression of Asporin mRNA and increased expression of bone and osteogenesis markers are detected compared to cells maintained without osteogenic induction. Importantly, treatment with human recombinant Asporin protein reduces the mineralization level in osteogenic media-induced aortic valvular interstitial cells with the concomitant decreased level of Wnt/&#x03B2;-catenin signaling. Overall, all these data are highly indicative that Asporin might be a novel biomolecular target to treat patients of calcific aortic valve disease over current cusp replacement surgery.

Anisha Polley

Riffat Khanam

Arunima Sengupta

Santanu Chakraborty

Asporin Reduces Adult Aortic Valve Interstitial Cell Mineralization Induced by Osteogenic Media and Wnt Signaling Manipulation In Vitro

Antiaging protein Klotho exhibits impressive properties of anti-inflammation, however is declined early after intervertebral disc injury, making Klotho restoration an attractive strategy of treating intervertebral disc inflammatory disorders. Here, we have found that Klotho is enriched in nucleus pulposus (NP) cells and Klotho overexpression attenuates H2O2-induced acute inflammation essentially via suppressing Toll-like receptor 4 (TLR4). The proinflammatory NF-&#x03BA;B signaling and cytokine expressions paralleled with Klotho repression and TLR4 elevation in both NP cells (H2O2 treatment) and rat intervertebral disc (needle puncture treatment). Overexpression of TLR4 downregulated expression of Klotho, whereas interfering TLR4 expression diminished the inhibitory effects of H2O2 on Klotho in NP cells. Consistently, Klotho knockdown by RNA interferences largely diminished the anti-inflammatory and intervertebral disc protective effects in an Intervertebral Disc Degeneration (IDD) model. Thus, our study indicates that TLR4-NF-&#x03BA;B signaling and Klotho form a negative-feedback loop in NP cells. Also, we demonstrate that the expression of Klotho is regulated by the balance between upregulation and downregulation of TLR4-NF-&#x03BA;B signaling.

Fangfang Bi

Wenbo Liu

Zongtao Wu

Chen Ji

Cuicui Chang

Antiaging Factor Klotho Retards the Progress of Intervertebral Disc Degeneration through the Toll-Like Receptor 4-NF-&#x03BA;B Pathway

Stem&#x002F;stromal cell-based therapies are a branch of regenerative medicine and stand as an attractive option to promote the repair of damaged or dysfunctional tissues and organs. Olfactory mucosa mesenchymal stem&#x002F;stromal cells have been regarded as a promising tool in regenerative therapies because of their several favorable properties such as multipotency, high proliferation rate, helpful location, and few associated ethical issues. These cells are easily accessible in the nasal cavity of most mammals, including the rat, can be easily applied in autologous treatments, and do not cope with most of the obstacles associated with the use of other stem cells. Despite this, its application in preclinical trials and in both human and animal patients is still limited because of the small number of studies performed so far and to the nonexistence of a standard and unambiguous protocol for collection, isolation, and therapeutic application. In the present work a validation of a protocol for isolation, culture, expansion, freezing, and thawing of olfactory mucosa mesenchymal stem&#x002F;stromal cells was performed, applied to the rat model, as well as a biological characterization of these cells. To investigate the therapeutic potential of OM-MSCs and their eventual safe application in preclinical trials, the main characteristics of OMSC stemness were addressed.

Rui D. Alvites

Mariana V. Branquinho

Ana R. Caseiro

Irina Amorim

S&#x00ED;lvia Santos Pedrosa

Alexandra R&#x00EA;ma

F&#x00E1;tima Faria

Beatriz Porto

Cl&#x00E1;udia Oliveira

Paula Teixeira

Rui Magalh&#x00E3;es

Stefano Geuna

Artur S. P. Varej&#x00E3;o

Ana C. Maur&#x00ED;cio

Rat Olfactory Mucosa Mesenchymal Stem&#x002F;Stromal Cells (OM-MSCs): A Characterization Study

Mitochondria change their morphology and distribution depending on the metabolism and functional state of a cell. Here, we analyzed the mitochondria and selected structures in female germ-line cysts in a representative of clitellate annelids &#x2013; the white worm Enchytraeus albidus in which each germ cell has one cytoplasmic bridge that connects it to a common cytoplasmic mass. Using serial block-face scanning electron microscopy (SBEM), we prepared three-dimensional ultrastructural reconstructions of the entire selected compartments of a cyst at the advanced stage of oogenesis, i.e. the nurse cell, cytophore, and cytoplasmic bridges of all 16 cells (15 nurse cells and oocyte). We revealed extensive mitochondrial networks in the nurse cells, cytophore and mitochondria that pass through the cytoplasmic bridges, which indicates that a mitochondrial network can extend throughout the entire cyst. The dynamic hyperfusion state was suggested for such mitochondrial aggregations. We measured the mitochondria distribution and revealed their polarized distribution in the nurse cells and more abundant accumulation within the cytophore compared to the nurse cell. A close association of mitochondrial networks with dispersed nuage material, which seems to be the structural equivalent of a Balbiani body, not described in clitellate annelids so far, was also revealed.

Anna Z. Urbisz

Sebastian Student

Ma&#x0142;gorzata A. &#x015A;liwi&#x0144;ska

Karol Ma&#x0142;ota

Morphology of Mitochondria in Syncytial Annelid Female Germ-Line Cyst Visualized by Serial Block-Face SEM

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International Journal of Cell Biology - Table of contents 2020

International Journal of Cell Biology | Hindawi

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International Journal of Cell Biology publishes original research articles as well as review articles in all areas of cell biology.

International Journal of Cell Biology

Table of Contents

Table of Contents: 2020

Asporin Reduces Adult Aortic Valve Interstitial Cell Mineralization Induced by Osteogenic Media and Wnt Signaling Manipulation In Vitro

Antiaging Factor Klotho Retards the Progress of Intervertebral Disc Degeneration through the Toll-Like Receptor 4-NF-κB Pathway

Rat Olfactory Mucosa Mesenchymal Stem/Stromal Cells (OM-MSCs): A Characterization Study

Morphology of Mitochondria in Syncytial Annelid Female Germ-Line Cyst Visualized by Serial Block-Face SEM