Chondropenia: current concept review

Abstract

The term "chondropenia" indicates the early stage of degenerative cartilage disease, and it has been identified by carefully monitoring early-stage osteoarthritis (OA). Not only is it the loss of articular cartilage volume, but it is also a rearrangement of biomechanical, ultrastructural, biochemical and molecular properties typical of healthy cartilage tissue. Diagnosing OA at an early stage or an advanced stage is valuable in terms of clinical and therapeutic outcome. In fact degenerative phenomena are supported by a complex biochemical cascade which unbalances the extracellular matrix homeostasis, closely regulated by chondrocytes. In the first stage an intense inflammatory reaction is triggered: pro-catabolic cytokines such as IL-1β and TNF-α triggering matrix metalloproteases and aggrecanase (ADAMT-4 and 5), responsible for the early loss of ultrastructural components, such as type II collagen and aggrecan. In addition nitric oxide and reactive oxygen species modulate the physiopathology of the condral matrix inducing apoptosis of chondrocytes through a mitochondria-dependent pathway. In addition, "Lonely Death": chondrocytes, are confined within a dense, avascular extracellular matrix capsule, and can trigger a genetically induced apoptosis and necrosis. The degenerative process starts from a central point and then spreads in a centrifugal manner in depth and in adjacent areas, eventually covering the whole joint; chondropenia represents a journey from the first clinically detectable time-point until it can be characterized as frank osteoarthritis. Currently, there are no instruments sensitive enough which allow a timely diagnosis of chondropenia. Innovative magnetic resonance imaging techniques, such as T2 mapping, can be effective and a sensitive diagnostic instrument for quantifying cartilage volume and proteoglycan content. However, avant-garde biophysical techniques, such as mechanical indenters, ultrasound and biochemical markers (uCTX-II), are rational and scientific tools applicable to the clinical and therapeutic management of early degenerative cartilage disease. The objective of this review on chondropenia is to present a state of the art and innovative concepts.

Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

“…During OA development, progressive cartilage degeneration is observed. Histochemistry analyses have demonstrated the formation of chondrocytes clusters, the presence of irregular surfaces (fibrillations), cartilage volume loss, and matrix calcification in OA cartilage compared to normal cartilage [18]. These changes in cartilage structure are linked to the alteration of molecular components of ECM.…”

“…Typically, the decrease in proteoglycan becomes prominent with disease progression and can be evidenced by reduced Safranin-O staining [19]. Distribution of the collagen II network is modified, being uniformly distributed throughout the normal cartilage layers, but at a decreased level in OA-degenerated areas and at an increased level in chondrocytes clusters [18]. Breakdown of these components are handled by a set of aggrecanases (e.g., a disintegrin and metalloproteinase with thrombospondin motifs ADAMTS-4 and -5) and collagenases (e.g., matrix metalloproteases, MMP-1, -3, -8, and -13), which are upregulated, even in early stages of OA-associated cartilage degradation.…”

Pharmacologic Interventions for Preventing Chondrocyte Apoptosis in Rheumatoid Arthritis and Osteoarthritis

“…Furthermore, changes in the number of viable articular chondrocytes in experimentally induced arthritis [99], human RA [100], and OA are almost certainly associated with the autophagicmediated cell death of chondrocytes [101][102][103][104][105], which occurs in concert with the activation of the extrinsic apoptosis pathway, the latter mediated by Tumor necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), Death Receptor-5 (DR5) and caspase-3 [106,107]. In that regard, it was noteworthy that Huang et al [108] reported that exogenous leptin promoted chondrocyte apoptosis while inhibiting chondrocyte autophagy via the up-regulation of lysyl oxidase-like 3 (LOXL3).…”

Mori Folium water extract alleviates articular cartilage damages and inflammatory responses in monosodium iodoacetate-induced osteoarthritis rats

“…Although various factors cause OA, aging is the most common factor associated with the development of OA; other factors, such as mechanical stress and hereditary and environmental factors, also lead to the development of OA ( 1 , 2 ). OA is primarily characterized by joint swelling due to a progressive breakdown and loss of articular cartilage, involving increased synovial inflammation, subchondral bone sclerosis and osteophyte formation, which leads to chronic pain and functional limitations in the joint ( 3 , 4 ). Furthermore, the dysregulation of glucose and energy metabolism also aggravate the symptoms in patients with OA ( 5 ).…”