This 2023 study treated human cartilage cells from knee replacement patients, all with a body mass index over 30, with leptin at 2 to 40 ng/ml, the range found in joint fluid. At 20 and 40 ng/ml, cartilage-building genes fell and ADAMTS5 rose. MMP13 rose only at 40 ng/ml.
Researchers took chondrocytes from areas of cartilage that looked normal, inside the knee joints of patients having knee replacement surgery, all with a BMI over 30. They treated the cells with leptin, a hormone made by fat tissue, at 2 to 40 ng/ml for 24 hours, and measured cartilage markers. They also turned the gene HES1 down or up to see whether it carried leptin's effects.
At 20 or 40 ng/ml, leptin lowered SOX9 and the SOX9-driven genes for type II collagen (COL2A1) and aggrecan (ACAN). HES1 fell and ADAMTS5 rose. Knocking down HES1 raised ADAMTS5, and boosting HES1 prevented the leptin-driven rise in ADAMTS5. MMP13 went up only at 40 ng/ml, and that rise did not depend on HES1. The authors note joint fluid leptin at this level is typically seen in people with metabolic syndrome and in women.
All donors had a BMI over 30 and were having knee replacements, so their cells may not behave like cells from other people. The abstract does not give the number of donors. Cells were treated for 24 hours, which says nothing about years of exposure. The study shows leptin can shift cartilage cells in a dish, not that it does so in a person's joint.
Leptin offers one possible link between metabolism and cartilage that goes beyond the load body weight puts on a joint. The study found the MMP13 rise only at the top of the tested range, while ADAMTS5 responded at lower levels, so the two enzymes do not always move together.
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