An integrated in silico-in vitro approach for identifying therapeutic targets against osteoarthritis

Background: Without the availability of disease-modifying drugs, there is an unmet therapeutic need for osteoarthritic patients. During osteoarthritis, the homeostasis of articular chondrocytes is dysregulated and a phenotypical transition called hypertrophy occurs, leading to cartilage degeneration. Targeting this phenotypic transition has...

Bioprinting of a Zonal-Specific Cell Density Scaffold: A Biomimetic Approach for Cartilage Tissue Engineering

The treatment of articular cartilage defects remains a significant clinical challenge. This is partially due to current tissue engineering strategies failing to recapitulate native organization. Articular cartilage is a graded tissue with three layers exhibiting different cell densities: the superficial zone having the highest density and the...

The Releasate of Avascular Cartilage Demonstrates Inherent Pro-Angiogenic Properties In Vitro and In Vivo

Objective: Cartilage is avascular and numerous studies have identified the presence of single anti- and pro-angiogenic factors in cartilage. To better understand the maintenance hyaline cartilage, we assessed the angiogenic potential of complete cartilage releasate with functional assays in vitro and in vivo. Design: We evaluated the gene...

Tyrosine kinases regulate chondrocyte hypertrophy: promising drug targets for Osteoarthritis

Osteoarthritis (OA) is a major health problem worldwide that affects the joints and causes severe disability. It is characterized by pain and low-grade inflammation. However, the exact pathogenesis remains unknown and the therapeutic options are limited. In OA articular chondrocytes undergo a phenotypic transition becoming hypertrophic, which...

Effect of Inflammatory Signaling on Human Articular Chondrocyte Hypertrophy: Potential Involvement of Tissue Repair Macrophages

Objective: In osteoarthritis, chondrocytes tend to acquire a hypertrophic phenotype, which contributes to the modification of the extracellular matrix, resulting in permanent cartilage changes. In mouse chondrocytes, pro-inflammatory macrophages and pro-inflammatory cytokines have been shown to stimulate hypertrophy via the activation of the...

Increased TGF-β and BMP Levels and Improved Chondrocyte-Specific Marker Expression In Vitro under Cartilage-Specific Physiological Osmolarity

During standard expansion culture (i.e., plasma osmolarity, 280 mOsm) human articular chondrocytes dedifferentiate, making them inappropriate for autologous chondrocyte implantation to treat cartilage defects. Increasing the osmolarity of culture media to physiological osmolarity levels of cartilage (i.e., 380 mOsm), increases collagen type...

An Instrument for Matching Defect and Implant Size in Matrix-induced Autologous Chondrocyte Implantation

Cartilage defects in the knee lead to limitations in the daily life of a large group of people in the worldwide population. Research on the treatment of cartilage injuries has lead to various clinical procedures, one of them being Matrix Induced Autologous Chondrocyte Implantation (MACI). MACI surgery consist of two procedures. During the first...

What quantitative mechanical loading stimulates in vitro cultivation best?

Articular cartilage has limited regeneration capacities. One of the factors that appear to affect the in vitro cultivation of articular cartilage is mechanical stimulation. So far, no combination of parameters has been identified that offers the best results. The goal is to review the literature in search of the best available set of...

Effect of Hypoxia on Transforming Growth Factor-beta Signaling Pathway in Osteoarthritic Human Cartilage

Objective: Due to avascularity, chondrocytes have poor ability to regenerate themselves which is challanging for tissue engineering to achieve full functioning cartilage. Culturing chondrocytes or cartilage tissue has been frequently perfomed by using atmospheric oxygen tensions which is hyperoxic compared to nature of healthy cartilage....