Strategies for Articular Cartilage Repair and Regeneration

Articular cartilage is an avascular tissue, with limited ability to repair and self-renew. Defects in articular cartilage can induce debilitating degenerative joint diseases such as osteoarthritis. Currently, clinical treatments have limited ability to repair, for they often result in the formation of mechanically inferior cartilage. In this review, we discuss the factors that affect cartilage homeostasis and function, and describe the emerging regenerative approaches that are informing the future treatment options.

Diagnostic and Therapeutic Role of Extracellular Vesicles in Articular Cartilage Lesions and Degenerative Joint Diseases

Two leading contributors to the global disability are cartilage lesions and degenerative joint diseases, which are characterized by the progressive cartilage destruction. Current clinical treatments often fail due to variable outcomes and an unsatisfactory long-term repair. Cell-based therapies were once considered as an effective solution because of their anti-inflammatory and immunosuppression characteristics as well as their differentiation capacity to regenerate the damaged tissue. However, stem cell-based therapies have inherent limitations, such as a high tumorigenicity risk, a low retention, and an engraftment rate, as well as strict regulatory requirements, which result in an underwhelming therapeutic effect. Therefore, the non-stem cell-based therapy has gained its popularity in recent years. Extracellular vesicles (EVs), in particular, like the paracrine factors secreted by stem cells, have been proven to play a role in mediating the biological functions of target cells, and can achieve the therapeutic effect similar to stem cells in cartilage tissue engineering. Therefore, a comprehensive review of the therapeutic role of EVs in cartilage lesions and degenerative joint diseases can be discussed both in terms of time and favorability. In this review, we summarized the physiological environment of a joint and its pathological alteration after trauma and consequent changes in EVs, which are lacking in the current literature studies. In addition, we covered the potential working mechanism of EVs in the repair of the cartilage and the joint and also discussed the potential therapeutic applications of EVs in future clinical use.

The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature

During the osteoarthritis (OA) process, activation of immune systems, whether innate or adaptive, is strongly associated with low-grade systemic inflammation. This process is initiated and driven in the synovial membrane, especially by synovium cells, themselves previously activated by damage-associated molecular patterns (DAMPs) released during cartilage degradation. These fragments exert their biological activities through pattern recognition receptors (PRRs) that, as a consequence, induce the activation of signaling pathways and beyond the release of inflammatory mediators, the latter contributing to the vicious cycle between cartilage and synovial membrane. The primary endpoint of this review is to provide the reader with an overview of these many molecules categorized as DAMPs and the contribution of the latter to the pathophysiology of OA. We will also discuss the different strategies to control their effects. We are convinced that a better understanding of DAMPs, their receptors, and associated pathological mechanisms represents a decisive issue for degenerative joint diseases such as OA.

Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes

Recent studies have shown that mesenchymal stem cells (MSCs) can play a restorative role against degenerative joint diseases in horses. The purpose of this study was to investigate whether fetal bone marrow-derived cells (BMC)-derived nanoparticles (BMC-NPs) can stimulate the survival of equine chondrocytes. Equine fetal BMCs were isolated and characterized, and the role of BMC-NPs s in equine chondrocytes undergoing inflammatory cell death was examined. BMCs have several characteristics, such as the potential to differentiate into chondrocytes and osteocytes. Additionally, BMCs expressed immunoregulatory genes in response to treatment with tumor necrosis factor-alpha (TNF-α) and Interleukin 1 beta (IL-1β). We found that BMC-NPs were taken up by equine chondrocytes. Functionally, BMC-NPs promoted the growth of chondrocytes, and reduced apoptosis induced by inflammatory cytokines. Furthermore, we observed that BMC-NPs upregulated the phosphorylation of protein kinase B (Akt) in the presence of IL-1β, and reduced the phosphorylation of TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the chondrocytes. Cumulatively, our study demonstrated that equine fetal BMC-NPs have the potential to stimulate the survival of chondrocytes damaged by inflammatory cytokines. Thus, BMC-NPs may become an alternative cell-free allogenic therapeutic for degenerative joint diseases in horses.

Sulfated Hyaluronan coating of polyurethanebased implant materials

Thermoplastic polycarbonate urethane elastomers (TPCU) are potential implant materials for treating degenerative joint diseases thanks to their adjustable rubberlike properties, their toughness, and their durability. We developed a water-containing high-molecular-weight sulfated hyaluronic acid-coating to improve the interaction of TPCU with the synovial fluid. It is suggested that trapped synovial fluid can act as a lubricant that reduces the friction forces and thus provides an enhanced abrasion resistance of TPCU implants. Aims of this work were (i) the development of a coating method for novel soft TPCU with high-molecular sulfated hyaluronic acid to increase the biocompatibility and (ii) the in vitro validation of the functionalized TPCUs in cell culture experiments.

Unilateral knee effusion in an elderly patient: an unusual presentation of rheumatoid arthritis

ABSTRACT Unilateral atraumatic knee effusion is a relatively common presenting complaint among geriatric patients in primary care and musculoskeletal speciality clinics. Gout, pseudogout, degenerative joint diseases and reactive arthritis are the most common causes of the atraumatic knee effusions. Rheumatoid arthritis very rarely presents as arthritis of one or two large joints. Arthrocentesis, plain radiography and screening blood tests should be performed to help narrow the differential diagnosis. In some cases, advanced imaging modalities such as MRI may be indicated. This study reports a case of rheumatoid arthritis in a 75-year-old gentleman with oligoarthropathy of two large joints as the presenting symptoms.