ABSTRACT
BACKGROUND: Progressive pseudorheumatoid dysplasia is a rare skeletal dysplasia mainly caused by abnormal autosomal recessive inheritance. Although the main function of cartilage is mechanical support and the characteristics of this disease is the degradation of AC, previous studies on it had been mainly focused on clinical and genetic aspects and the mechanical behavior of the cartilage affected by PPRD is still ambiguous. In this study, we investigate the mechanics and structure of the cartilage suffered disease at multi-scale, from individual chondrocytes to the bulk-scale tissue. METHODS: Depth-sensing indenter were employed to investigate the mechanics of cartilage; we performed atomic force microscope nanoindentation to investigate the cell mechanics and scanning electron microscopy were used to explore the structure feature and chemical composition. FINDINGS: The elastic modulus of chondrocytes harvested from cartilage suffered from progressive pseudorheumatoid dysplasia is significantly higher than from normal cartilage, same trend were also found in tissue level. Moreover, denser collagen meshwork and matrix calcification were also observed. INTERPRETATION: The elastic modulus of cartilage should closely related to its denser structure and the calcification, and may potentially be an indicator for clinical diagnosis. The stiffening of chondrocytes during PPRD progression should play a rather important role in its pathogenesis.
Subject(s)
Cartilage, Articular/pathology , Disease Progression , Joint Diseases/congenital , Mechanical Phenomena , Biomechanical Phenomena , Cartilage, Articular/metabolism , Chondrocytes/metabolism , Chondrocytes/pathology , Collagen/metabolism , Elastic Modulus , Humans , Joint Diseases/metabolism , Joint Diseases/pathologyABSTRACT
Osteoarthritis (OA) is a prevalent joint disorder worldwide. Recent studies suggested that macrophages play an important role in the progression of OA. However, the detailed pathology related to macrophages is still ambiguous, especially where related to mechanotransduction. In this study, polycaprolactone (PCL) and Eucommia Ulmoides Gum (EUG) composite scaffolds were first fabricated by electrospinning. The stiffness of as-fabricated scaffolds was altered by adjusting the PCL-to-EUG ratio. The mechanical properties, structural characteristics and chemical composition of the scaffolds were investigated using various materials characterization techniques. The results show that stiffness of the scaffolds was in the same range as that of cartilage tissues with OA. Confocal microscopy and reverse transcription-polymerase chain reaction (RT-PCR) were performed to investigate the macrophages cultured on the scaffolds. Significant morphological changes of cells were observed on PCL/EUG scaffolds with different stiffness. The expression of inflammatory and fibrosis-related cytokines increases as scaffold stiffness decreases, similar to the trend observed in OA progression.
Subject(s)
Eucommiaceae/chemistry , Macrophages/drug effects , Macrophages/metabolism , Mechanical Phenomena/drug effects , Plant Gums/chemistry , Polyesters/chemistry , Polyesters/pharmacology , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biomechanical Phenomena/drug effects , Cell Survival/drug effects , Macrophages/cytology , Mice , RAW 264.7 CellsABSTRACT
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.pbiomolbio.2018.05.008. The duplicate article has therefore been withdrawn.
