## 1 Introduction  
Osteoarthritis (OA) is a degenerative pathology of the joints, affecting the entire joint: cartilage, synovium, subchondral bone, meniscus, ligaments, joint capsule and soft tissues. The risk factors that lead to its occurrence are advanced age, joint trauma, obesity, and overuse. The main symptoms are pain and functional impotence, swelling and joint instability. In the advanced stages of the disease, the symptoms limit the activity of patients, with serious effects on the physical and mental health of the patient, as well as economic and social aspects [1]. Articular cartilage is a specialized connective tissue made up of chondrocytes that produce collagen, proteoglycans, and elastin fibers essential for maintaining the integrity of the joint [2]. Articular cartilage is a connective tissue that lines the bone at the joints, with the function of lubricating the smooth surface and facilitating movement. Articular cartilage has a limited capacity for healing because it lacks nerves and blood vessels; therefore, maintaining intact articular cartilage is important in preventing OA [3]. One specific characteristic of osteoarthritis consists of collagen synthesis/collagen degradation imbalance. The production of proinflammatory and fibrotic mediators which are involved in an inflammation process is generated by the reaction of macrophages and fibroblast-like synovioocytes with molecules in damaged hyaline cartilage [4]. Synovial inflammation will increase the production of proinflammatory cytokines, such as IL-6, tumor necrosis factor (TNF) and prostagland landins that contribute to cartilage degradation and exacerbate joint damage [5]. IL-6, a proinflammatory mediator, is actively involved in the development of OA. Elevated serum or synovial fluid levels in patients with OA are associated with increased incidence and severity of the disease. IL-6 induces matrix-degrading enzymes, thereby significantly contributing to the cartilage pathology development. However, it is also involved in the anti-catabolic factors expression with a protective role [6]. Tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)) and IL-6 indirectly induce osteoclastogenesis through the RANK/RANKL signaling pathway. Increased RANKL in the cartilage matrix allows its binding to its receptor, RANK, on the surface of preosteoclasts, which will determine the production of mature osteoclasts responsible for resorbing subchondoral bone and will implicitly lead to the appearance of osteochondritis [7]. RANK/RANKL signaling pathway presents a specific role in osteoclast differentiation and activation, and it is therefore considered an important factor in the occurrence and progression of OA. Elevated RANKL levels in the cartilage matrix trigger many molecular events, causing progressive cartilage damage. The receptor from the preosteoclast cells surface (RANK) is bind by its ligand (RANKL), causing cells differentiation and maturation [8]. Another important biomarker, hydroxproline, is an amino acid that represents one of the main components of the collagen protein, ensuring the stability and shape of the cartilage [9]. The important influence of those biomarkers in the OA development is represented in Scheme 1. Collagenase is an enzyme that acts on the peptide bonds in collagen, breaking them. Intra-articular injection of collagenase leads to the degradation of articular collagen, which causes the appearance of OA, which gradually sets in 6 weeks after the injection of two doses of 500 U of collagenase. Then, clear signs of OA appear, such as deep erosions of the cartilage matrix with areas of exposure of the subchondral bone, cartilage cracks with hypertrophy and inflammation of the synovium [10]. Currently, the main treatment methods for OA focus on combating pain, and they are mainly represented by anti-inflammatory and anti-allergic medication which can present a series of adverse reactions; however, they focus on treating the symptoms and not the cause [11].