Abstract
Degenerative diseases of cartilaginous tissues in joints often lead to major clinical problems. Osteoarthritis (OA) is a debilitating joint disease wherein articular cartilage gradually deteriorates, affecting 7% of the global population [1]. Degeneration of the intervertebral disk is closely associated with low-back pain that afflicts millions of individuals all over the world [2]. The temporomandibular joint disorders are a common source of chronic orofacial pain that afflicts 3.6% to 7% of the population [3]. OA of the temporomandibular joint is one of the major etiological factors for temporomandibular joint disorders [4]. Clearly, degeneration of cartilaginous tissues represents significant health and economic concerns worldwide.
Degenerative joint diseases are characterized as inflammatory diseases [5 –7]. Several proinflammatory cytokines, mainly interleukin-1β and tumor necrosis factor-α, are present at elevated concentrations in the arthritic joints and degenerated disks [5 –7]. Proinflammatory cytokines often promote catabolic activities (eg, production of extracellular matrix-degrading enzymes) and induce apoptosis [5 –8]. Increased activities of extracellular matrix-degrading enzymes weaken the integrity and mechanical function of extracellular matrix, resulting in detrimental mechanical microenvironment that could further damage cells.
Furthermore, the avascular nature of cartilaginous tissues, such as articular cartilage and intervertebral disks, provides minimal access to progenitor reparative cells, thereby nearly eliminating their regenerative capabilities. Thus, the inflammatory conditions in degenerative joint diseases can further reduce the limited self-regenerative capability of cartilaginous tissues, facilitating progress of tissue degeneration.
Chondrogenesis is a well-orchestrated process by which condensed progenitor cells differentiate into chondrocytes and secrete extracellular matrix molecules that form cartilaginous tissues. Owing to the chondrogenic abilities of embryonic, adult, and induced pluripotent stem cells [9], stem cell therapy for degenerative joint diseases has gained significant attention. Furthermore, it has been shown that various paracrine factors and extracellular vesicles (eg, exosomes) secreted by stem cells can enhance cell proliferation and inhibit apoptosis and inflammation [10,11], which can promote the healing process of disease or damaged cartilaginous tissues. Therefore, recent advances in stem cell research provide great promise for developing effective therapies that can repair or regenerate diseased or damaged cartilaginous tissues.
In this special issue, new concepts in development of temporomandibular joint OA, in vitro OA model, treatment strategies of disk degeneration, efficacy of stem cell therapy for OA, and mechanobiology of stem cells are reviewed, and research reports on stem cell therapy of bone marrow lesions and chondroprotective effects of stem cell secretomes are presented.
Animal models often used to study OA cannot fully mimic biology and anatomy of human articular cartilage or serve as patient-specific models of disease, which leads to clinically inconsistent therapeutics. Wu and Vunjak-Novakovic highlighted human-induced pluripotent stem cells as the advantageous cell source for developing in vitro OA models that could recapitulate physiological interactions with human cells and disease-initiating factors.
Regenerative cellular therapies have been increasingly popular for repair and regeneration of articular cartilage in OA knee joints. Although numerous systematic reviews (SRs) and meta-analyses (MAs) have been published to compare the efficacy and safety of stem cell therapy for treating knee OA, the methodological quality and risk of bias of those SRs/MAs have been poorly investigated. Liu et al. provided a rigorous evaluation on the methodological quality and risk of bias in SRs/MAs of stem cell therapy for knee OA.
Mandibular condylar cartilage, a typical fibrocartilage, has become a research focus in recent years because of its unique pathophysiological responses during development of temporomandibular joint OA. However, the etiology, pathogenic processes, and regulatory mechanisms of this disease are still unclear. Xu et al. summarized the current research progress on the cell subsets of mandibular condylar cartilage from the perspective of development and degeneration of mandibular condylar cartilage.
Owing to high mechanical demand, articular cartilage or intervertebral disk is subjected to various forms of mechanical loading (eg, shear, tensile, and compressive loading, and hydrostatic and osmotic pressure) that could modulate cellular metabolism in the tissues. Volz et al. summarized the mechanobiological stimulation of stem cell chondrogenesis and methodological approaches utilized to date to promote chronogenesis of stem cells in vitro.
The subchondral bone underneath articular cartilage is responsible for cartilage nutrition and plays an essential role in the healing of chondral defects. Bone marrow lesions are focal pathological changes in the subchondral bone that correlate with OA. However, treatment options for subchondral bone are limited. Dallo et al. presented a new minimally invasive procedure for treating symptomatic bone marrow lesions using bone marrow aspirate.
Although stem cells offer considerable potential for repair and regeneration of degenerative cartilaginous tissues, the inflammatory conditions in degenerative joint diseases represent a major obstacle to successful tissue repair. Previous studies have demonstrated that pentosan polysulfate suppresses inflammatory responses and enhances chondrogenic differentiation of stem cells. The review by Smith et al. outlined the potential of pentosan polysulfate to improve the stem cells therapy of disk degeneration. Finally, the study of Beatty et al. demonstrated that milk fat globule-epidermal growth factor 8 is an effective anti-inflammatory agent contributing to the chondroprotective effects of periodontal ligament-derived stem cell secretome on acutely injured articular cartilage.