Abstract
As the most common chronic degenerative joint disease, osteoarthritis (OA) is the leading cause of pain and physical disability, affecting millions of people worldwide. Mainly characterized by articular cartilage degradation, osteophyte formation, subchondral bone remodeling, and synovial inflammation, OA is a heterogeneous disease that impacts all component tissues of the articular joint organ. Pathological changes, and thus symptoms, vary from person to person, underscoring the critical need of personalized therapies. However, there has only been limited progress towards the prevention and treatment of OA, and there are no approved effective disease-modifying osteoarthritis drugs (DMOADs). Conventional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy, are still the major remedies to manage the symptoms until the need for total joint replacement. In this review, we provide an update of the known OA risk factors and relevant mechanisms of action. In addition, given that the lack of biologically relevant models to recapitulate human OA pathogenesis represents one of the major roadblocks in developing DMOADs, we discuss current in vivo and in vitro experimental OA models, with special emphasis on recent development and application potential of human cell-derived microphysiological tissue chip platforms.
Highlights
Existing since ancient times and officially named and defined in the 19th century [1], osteoarthritis (OA) has been the most common degenerative joint disease
These results reveal the importance of WNT signaling in maintaining the normal function of chondrocytes and suggest a potential detrimental effect of Wnt inhibitor-based disease-modifying osteoarthritis drugs (DMOADs) on articular cartilage homeostasis and OA progression [96,99]
In a study to explore the crosstalk between tissue components of the joint organ, subsequent to injurious insults, we examined the interactions between the infrapatellar fat pad (IPFP) and articular cartilage, before and after mechanical trauma
Summary
Existing since ancient times and officially named and defined in the 19th century [1], osteoarthritis (OA) has been the most common degenerative joint disease. OA presents with joint space narrowing, osteophytosis, subchondral sclerosis, cyst formation, and abnormalities of bone contour [10,11] These changes cause pain, stiffness, tenderness, and loss of mobility that often arise near the end of disease progression, greatly impacting patients’ life quality and even leading to mortality [12]. Several of cellular agingdefects have been involves and age-related diseases [27,28] Sources of this damage are primarily reactive oxygen andover nitrogen the accumulation of random unrepaired molecular damage to DNA, proteins, and lipids time species produced by mitochondria and cellular stress responses, respectively. The proximal effect of these reactive oxygen species (ROS) is the accumulation of somatic mutations and DNA damage, telomere changes reduce the ability of chondrocytes to main cartilage homeostasis and lower the threshold of damage-inducing load [29]. The exact contribution of aging-associated chondrocyte senescence to OA pathogenesis requires further investigation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
