Tibial bone transport using external fixation in adults: a systematic review.

Osteoarthritis, the most prevalent form of arthritis, is a chronic degenerative complex disease that is projected to affect over one billion individuals worldwide by 2050. Osteoarthritis is characterized by progressive breakdown of articular cartilage and low-grade inflammation of the surrounding tissues, leading to pain, stiffness, and reduced mobility. It most commonly affects the knee, hand, and hip joints. In addition to risk factors such as age, obesity, and joint injury, osteoarthritis also has a genetic risk component. Currently, there is no effective disease-modifying treatment for osteoarthritis, and strategies focus on pain management and joint replacement surgery. Therefore, there is an urgent need for an in-depth understanding of the processes underpinning osteoarthritis to foster the development of new therapies. Genome-wide association studies (GWAS) have identified over 960 independent risk variants for osteoarthritis, the majority of which reside in non-coding regions of the genome. Thus, the key challenge is to identify the effector genes through which these associated variants affect osteoarthritis risk. Osteoarthritis is a whole-joint disease, driven by a complex interplay of both shared and tissue-specific mechanisms. Shared mechanisms involve inflammatory pathways, biomechanical stress, and metabolic imbalances that collectively contribute to the degeneration of articular cartilage, the primary hallmark of osteoarthritis. This includes extensive changes in the extracellular matrix (ECM), including loss of proteoglycans and collagen through enzymatic cleavage, mediated by metalloproteinases and aggrecanases, and loss of chondrocyte ECM maintenance properties through senescence and apoptosis. In addition to cartilage degradation, osteoarthritis affects the synovium, subchondral bone, and fat pad tissues. The synovium commonly exhibits inflammation (synovitis) characterized by increased production of pro-inflammatory cytokines, contributing to cartilage degradation and joint inflammation. Pro-inflammatory cytokines are also secreted by the adipose tissue located in the infrapatellar fat pad. There is evidence that crosstalk between the synovium and fat pad could stimulate the infiltration of immune cells and the secretion of catabolic molecules across both tissues. Subchondral bone undergoes abnormal remodeling and sclerosis, influenced by altered bone turnover and microdamage repair processes. These interconnected pathophysiological changes underscore the importance of studying multiple primary tissues. Expression quantitative trait loci (eQTLs) capture the association between genetic variation and tissue-specific gene expression (proximal or distal). The regulatory relationships captured by eQTLs can generate hypotheses for the function of disease-associated variants identified through GWAS. Given the tissue- and context-specificity underlying gene regulatory patterns, eQTL regulatory relationships are best captured in the context of the studied phenotype in the primary affected tissue(s).