Molecular Insights Into Lysyl Oxidases in Cartilage Regeneration and Rejuvenation

Abstract

Articular cartilage remains among the most difficult tissues to regenerate due to its poor self-repair capacity. The lysyl oxidase family (LOX; also termed as protein-lysine 6oxidase), mainly consists of lysyl oxidase (LO) and lysyl oxidase-like 1-4 (LOXL1-LOXL4), has been traditionally defined as cuproenzymes that are essential for stabilization of extracellular matrix, particularly cross-linking of collagen and elastin. LOX is essential in the musculoskeletal system, particularly cartilage. LOXs-mediated collagen cross-links are essential for the functional integrity of articular cartilage. Appropriate modulation of the expression or activity of certain LOX members selectively may become potential promising strategy for cartilage repair. In the current review, we summarized the advances of LOX in cartilage homeostasis and functioning, as well as copper-mediated activation of LOX through hypoxia-responsive signaling axis during recent decades. Also, the molecular signaling network governing LOX expression has been summarized, indicating that appropriate modulation of hypoxia-responsive-signaling-directed LOX expression through manipulation of bioavailability of copper and oxygen is promising for further clinical implications of cartilage regeneration, which has emerged as a potential therapeutic approach for cartilage rejuvenation in tissue engineering and regenerative medicine. Therefore, targeted regulation of copper-mediated hypoxiaresponsive signalling axis for selective modulation of LOX expression may become potential effective therapeutics for enhanced cartilage regeneration and rejuvenation in future clinical implications.

Severe Spinal Cord Injury in Rats Induces Chronic Changes in the Spinal Cord and Cerebral Cortex Metabolism, Adjusted by Thiamine That Improves Locomotor Performance

“…A higher availability of free lysine in the SCI-affected brain may be useful due to excessive modification of the protein lysine residues by endogenous acrolein rising in SCI ( Zheng et al, 2013 ). Besides, free lysine may regulate the NO ⋅ generation ( Boyko et al, 2018 ) and inhibit the protein lysyl oxidases potentially involved in the neurotrauma-associated modification of extracellular matrix and inflammation ( Lin et al, 2020 ). Lysine also generates polyamines that are part of the stress response systems in living organisms ( Olin-Sandoval et al, 2019 ; Sakamoto et al, 2020 ; Wu et al, 2020 ).…”

Characterization of Properties, In Vitro and In Vivo Evaluation of Calcium Phosphate/Amino Acid Cements for Treatment of Osteochondral Defects

“…In the case of CAK and CAL cements, the amino acid composition with LYS had a more positive effect on osteogenic activity of osteoblasts than mixture with ARG [ 73 ]. Note that LYS plays the crucial role in the cross-linking of the collagen fibers [ 74 ].…”

Deer antler extract potentially facilitates xiphoid cartilage growth and regeneration and prevents inflammatory susceptibility by regulating multiple functional genes

“…Acan, a critical proteoglycan component for cartilage structure, is indispensable not only for the formation of cartilage in development but also for the maintenance of cartilage after maturation [ 34 ]. Loxl4 is a family member of lysyl oxidases that play crucial roles in the maintenance of cartilage function and cartilage regeneration [ 35 ]. Cyr61, also known as cellular communication network factor 1 (Cnn1), has the capacity to promote cartilage regeneration by facilitating chondrocyte cloning in osteoarthritic cartilage [ 36 ].…”