The immune microenvironment in cartilage injury and repair

The ability of articular cartilage to repair itself is limited because it lacks blood vessels, nerves, and lymph tissue. Once damaged, it can lead to joint swelling and pain, accelerating the progression of osteoarthritis. To date, complete regeneration of hyaline cartilage exhibiting mechanical properties remains an elusive goal, despite the many available technologies. The inflammatory milieu created by cartilage damage is critical for chondrocyte death and hypertrophy, extracellular matrix breakdown, ectopic bone formation, and progression of cartilage injury to osteoarthritis. In the inflammatory microenvironment, mesenchymal stem cells (MSCs) undergo aberrant differentiation, and chondrocytes begin to convert or dedifferentiate into cells with a fibroblast phenotype, thereby resulting in fibrocartilage with poor mechanical qualities. All these factors suggest that inflammatory problems may be a major stumbling block to cartilage repair. To produce a milieu conducive to cartilage repair, multi-dimensional management of the joint inflamma -tory microenvironment in place and time is required. Therefore, this calls for elucidation of the immune microenvironment of cartilage repair after injury. This review provides a brief overview of: (1) the patho-genesis of cartilage injury; (2) immune cells in cartilage injury and repair; (3) effects of inflammatory cytokines on cartilage repair; (4) clinical strategies for treating cartilage defects; and (5) strategies for targeted immunoregulation in cartilage repair. Statement of SignificanceImmune response is increasingly considered the key factor affecting cartilage repair. It has both nega-tive and positive regulatory effects on the process of regeneration and repair. Proinflammatory factors are secreted in large numbers, and necrotic cartilage is removed. During the repair period, immune cells can secrete anti-inflammatory factors and chondrogenic cytokines, which can inhibit inflammation and promote cartilage repair. However, inflammatory factors persist, which accelerate the degradation of the cartilage matrix. Furthermore, in an inflammatory microenvironment, MSCs undergo abnormal differen-tiation, and chondrocytes begin to transform or dedifferentiate into fibroblast-like cells, forming fibrocar-tilage with poor mechanical properties. Consequently, cartilage regeneration requires multi-dimensional regulation of the joint inflammatory microenvironment in space and time to make it conducive to carti-lage regeneration. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

The limited ability of articular cartilage to repair itself is hindered by inflammatory problems. Immune response plays a crucial role in both promoting cartilage repair and accelerating cartilage degradation. Multi-dimensional regulation of the inflammatory microenvironment is needed for cartilage regeneration.