Regulation of Chondrocyte Differentiation by Changing Intercellular Distances Using Type II Collagen Microfibers

Osteoarthritis is a common degenerative disease that mainly occurs in older age groups, and the search for an effective cure remains a major global challenge. The technology of constructing 3D in vitro cartilage tissue with zonal differentiated structures for use as alternative implants for treating osteoarthritis has attracted researchers’ attention. For this challenge, it is important for understanding the relationship between chondrocyte differentiation and the amount of extracellular matrix by modulating intercellular distance. This study investigates the interplay between chondrocyte differentiation and intercellular distance. Type II collagen microfibers (CMF II) were used as a distance regulator by varying their amounts. The results indicated that the secretion of cartilage-specific glycosaminoglycan after 2 weeks of differentiation from the chondrogenic cells, ATDC5, was decreased with an increased intercellular distance. Also, the shortest intercellular distance, being ATDC5 cells without CMF II, presented an upregulated gene expression profile of cartilage markers. The groups with CMF II-mediated intracellular distances, however, did not show the upregulation. The elastic modulus of the 3D samples increased depending on the amount of CMF II, relating to the differentiation preventing property of the CMF II. These findings suggest the promising potential of this approach for the modulation of chondrocyte differentiation

Regulation of Chondrocyte Differentiation by Changing Intercellular Distances Using Type II Collagen Microfibers

Osteoarthritis is a common degenerative disease that mainly occurs in older age groups, and the search for an effective cure remains a major global challenge. The technology of constructing 3D in vitro cartilage tissue with zonal differentiated structures for use as alternative implants for treating osteoarthritis has attracted researchers’ attention. For this challenge, it is important for understanding the relationship between chondrocyte differentiation and the amount of extracellular matrix by modulating intercellular distance. This study investigates the interplay between chondrocyte differentiation and intercellular distance. Type II collagen microfibers (CMF II) were used as a distance regulator by varying their amounts. The results indicated that the secretion of cartilage-specific glycosaminoglycan after 2 weeks of differentiation from the chondrogenic cells, ATDC5, was decreased with an increased intercellular distance. Also, the shortest intercellular distance, being ATDC5 cells without CMF II, presented an upregulated gene expression profile of cartilage markers. The groups with CMF II-mediated intracellular distances, however, did not show the upregulation. The elastic modulus of the 3D samples increased depending on the amount of CMF II, relating to the differentiation preventing property of the CMF II. These findings suggest the promising potential of this approach for the modulation of chondrocyte differentiation

Regulation of Chondrocyte Differentiation by Changing Intercellular Distances Using Type II Collagen Microfibers

Osteoarthritis is a common degenerative disease that mainly occurs in older age groups, and the search for an effective cure remains a major global challenge. The technology of constructing 3D in vitro cartilage tissue with zonal differentiated structures for use as alternative implants for treating osteoarthritis has attracted researchers’ attention. For this challenge, it is important for understanding the relationship between chondrocyte differentiation and the amount of extracellular matrix by modulating intercellular distance. This study investigates the interplay between chondrocyte differentiation and intercellular distance. Type II collagen microfibers (CMF II) were used as a distance regulator by varying their amounts. The results indicated that the secretion of cartilage-specific glycosaminoglycan after 2 weeks of differentiation from the chondrogenic cells, ATDC5, was decreased with an increased intercellular distance. Also, the shortest intercellular distance, being ATDC5 cells without CMF II, presented an upregulated gene expression profile of cartilage markers. The groups with CMF II-mediated intracellular distances, however, did not show the upregulation. The elastic modulus of the 3D samples increased depending on the amount of CMF II, relating to the differentiation preventing property of the CMF II. These findings suggest the promising potential of this approach for the modulation of chondrocyte differentiation

C9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits

Objective: How hexanucleotide (GGGGCC) repeat expansions in C9ORF72 cause amyotrophic lateral sclerosis (ALS) remains poorly understood. Both gain- and loss-of-function mechanisms have been proposed. Evidence supporting these mechanisms in vivo is, however, incomplete. Here we determined the effect of C9orf72 loss-of-function in mice. Methods: We generated and analyzed a conditional C9orf72 knockout mouse model. C9orf72fl/fl mice were crossed with Nestin-Cre mice to selectively remove C9orf72 from neurons and glial cells. Immunohistochemistry was performed to study motor neurons and neuromuscular integrity, as well as several pathological hallmarks of ALS, such as gliosis and TDP-43 mislocalization. In addition, motor function and survival were assessed. Results: Neural-specific ablation of C9orf72 in conditional C9orf72 knockout mice resulted in significantly reduced body weight but did not induce motor neuron degeneration, defects in motor function, or altered survival. Interpretation: Our data suggest that C9orf72 loss-of-function, by itself, is insufficient to cause motor neuron disease. These results may have important implications for the development of therapeutic strategies for C9orf72-associated ALS