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Updated: Mar 15, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Reduced Osteoarthritis Severity in Aged Mice With Deletion of Macrophage Migration Inhibitory Factor
Meredith A Rowe1, Lindsey R Harper2, Margaret A McNulty3
1Wake Forest School of Medicine, Winston-Salem, North Carolina, and University of North Carolina at Chapel Hill.
Objective:
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is elevated in the serum and synovial fluid of patients with osteoarthritis (OA). This study was undertaken to investigate the potential role of MIF in OA in human joint tissues and in vivo in mice with age-related and surgically induced OA.
Methods:
MIF in conditioned media from human chondrocytes and meniscal cells and from cartilage explants was measured by enzyme-linked immunosorbent assay. The severity of OA was analyzed histologically in male wild-type and MIF-/- mice at 12 and 22 months of age and following destabilization of the medial meniscus (DMM) surgery in 12-week-old MIF-/- mice as well as in wild-type mice treated with a neutralizing MIF antibody. Synovial hyperplasia was graded in S100A8-immunostained histologic sections. Bone morphometric parameters were measured by micro-computed tomography.
Results:
Human OA chondrocytes secreted 3-fold higher levels of MIF than normal chondrocytes, while normal and OA meniscal cells produced equivalent amounts. Compared to age- and strain-matched controls, the cartilage, bone, and synovium in older adult mice with MIF deletion were protected against changes of naturally occurring age-related OA. No protection against DMM-induced OA was seen in young adult MIF-/- mice or in wild-type mice treated with anti-MIF. Increased bone density in 8-week-old mice with MIF deletion was not maintained at 12 months.
Conclusion:
These results demonstrate a differential mechanism in the pathogenesis of naturally occurring age-related OA compared to injury-induced OA. The inhibition of MIF may represent a novel therapeutic target in the reduction of the severity of age-related OA.
Insights
Macrophage migration inhibitory factor (MIF) protects against age-related osteoarthritis (OA) in mice. However, MIF inhibition did not prevent surgically induced OA, suggesting different therapeutic targets for OA types.
Area of Science:
- Biomedical Science
- Immunology
- Orthopedics
Background:
- Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine implicated in osteoarthritis (OA).
- Elevated MIF levels are observed in OA patients' serum and synovial fluid.
- The precise role of MIF in OA pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the role of MIF in human joint tissues and mouse models of OA.
- To compare MIF's role in age-related OA versus surgically induced OA.
- To assess the therapeutic potential of MIF inhibition in OA.
Main Methods:
- MIF levels were measured in human chondrocytes and meniscal cells.
- Histological analysis of OA severity in wild-type and MIF-deficient mice at different ages.
- Evaluation of surgically induced OA (DMM model) in MIF-deficient mice and wild-type mice treated with anti-MIF antibody.
- Assessment of synovial hyperplasia and bone morphometry.
Main Results:
- Human OA chondrocytes secreted significantly higher MIF levels than normal chondrocytes.
- Mice lacking MIF exhibited protection against age-related OA, including cartilage, bone, and synovium.
- MIF deficiency or antibody treatment did not protect against surgically induced OA.
- Transiently increased bone density in young MIF-deficient mice was not sustained.
Conclusions:
- MIF plays a distinct role in age-related OA pathogenesis compared to injury-induced OA.
- Targeting MIF may be a viable therapeutic strategy for age-related OA.
- Further research is needed to differentiate therapeutic approaches for various OA subtypes.
