The spatial organisation of joint surface chondrocytes: review of its potential roles in tissue functioning, disease and early, preclinical diagnosis of osteoarthritis

Abstract

Chondrocytes display within the articular cartilage depth-dependent variations of their many properties that are comparable to the depth-dependent changes of the properties of the surrounding extracellular matrix. However, not much is known about the spatial organisation of the chondrocytes throughout the tissue. Recent studies revealed that human chondrocytes display distinct spatial patterns of organisation within the articular surface, and each joint surface is dominated in a typical way by one of four basic spatial patterns. The resulting complex spatial organisations correlate with the specific diarthrodial joint type, suggesting an association of the chondrocyte organisation within the joint surface with the occurring biomechanical forces. In response to focal osteoarthritis (OA), the superficial chondrocytes experience a destruction of their spatial organisation within the OA lesion, but they also undergo a defined remodelling process distant from the OA lesion in the remaining, intact cartilage surface. One of the biological insights that can be derived from this spatial remodelling process is that the chondrocytes are able to respond in a generalised and coordinated fashion to distant focal OA. The spatial characteristics of this process are tremendously different from the cellular aggregations typical for OA lesions, suggesting differences in the underlying mechanisms. Here we summarise the available information on the spatial organisation of chondrocytes and its potential roles in cartilage functioning. The spatial organisation could be used to diagnose early OA onset before manifest OA results in tissue destruction and clinical symptoms. With further development, this concept may become clinically suitable for the diagnosis of preclinical OA.

Onset and Progression of Human Osteoarthritis—Can Growth Factors, Inflammatory Cytokines, or Differential miRNA Expression Concomitantly Induce Proliferation, ECM Degradation, and Inflammation in Articular Cartilage?

“…As discussed, proliferation-induced changes in the SCSO of human AC and formation of cell clusters are early OA marker [10,14]. Increased expression of the proliferation markers cyclin D1 ( CCDN1 ) and cyclin dependent kinase 6 (CDK6) has been observed in human OA AC compared to healthy control AC [142].…”

“…Of particular interest, it has been shown that, when human AC samples are fluorescence-tagged and viewed from above, the cells exhibit complex patterns of arrangement in the surface layer of the superficial zone and with an orientation parallel to the joint surface, a feature that has been called superficial cell spatial organization (SCSO) [10,11]. The human SCSO can be highly dynamic, as horizontally orientated cell strings, for example in intact knee AC progress in early OA into double strings, together with an increased SZ cell density suggesting AC cell proliferation, are typical [12].…”

“…The human SCSO can be highly dynamic, as horizontally orientated cell strings, for example in intact knee AC progress in early OA into double strings, together with an increased SZ cell density suggesting AC cell proliferation, are typical [12]. With OA progression, cell clusters occur, which are ultimately succeeded by a diffuse cell arrangement that is lacking any discernable organization [10,13]. A hallmark of early OA is proliferation of AC-inherent cells [10,13,14], which can be linked to these predictable SCSO changes (see Figure 1) through experimentally inducing AC cell proliferation in early OA AC explants beneath the joint surface.…”

“…With OA progression, cell clusters occur, which are ultimately succeeded by a diffuse cell arrangement that is lacking any discernable organization [10,13]. A hallmark of early OA is proliferation of AC-inherent cells [10,13,14], which can be linked to these predictable SCSO changes (see Figure 1) through experimentally inducing AC cell proliferation in early OA AC explants beneath the joint surface. Indeed, proliferation induced via fibroblast growth factor 2 (FGF2) recapitulated SCSO loss and generated a structural AC phenotype that was comparable to advanced OA [13]: human AC explants containing strings and early OA-typical double strings oriented parallel to the surface altered their SCSO through induced proliferation into a diffuse arrangement lacking any discernable organization.…”

Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling

“…Osteoarthritis (OA) is characterized by the degeneration of articular cartilage and subchondral bone and accompanied by joint pain, swelling and stiffness, leading to joint dysfunction [1,2]. Many different factors, including genetics, lifestyle and joint instability contribute to the onset and progression of OA, which greatly affects quality of life in elder population [3].…”