This 2003 lab study treated cartilage cells from the knees of people with osteoarthritis with glucosamine sulphate at 0.2 to 200 µM. Aggrecan core protein rose with dose, MMP-3 fell by 18 to 65%, and cell-associated glycosaminoglycans rose by 25 to 140%. Cells from 40% of patients did not respond.
Researchers isolated chondrocytes from the knee cartilage of patients with osteoarthritis and cultured them with glucosamine sulphate at concentrations from 0.2 to 200 µM. They measured aggrecan and MMP-3 protein in the culture medium by Western blot, MMP-3 enzyme activity by zymography, aggrecan and MMP-3 messenger RNA by Northern blot, and glycosaminoglycans in the cell layer.
Between 1.0 and 150 µM, glucosamine sulphate raised aggrecan core protein in a dose-dependent way, reaching 120% at 150 µM, with a matching rise in aggrecan messenger RNA. MMP-3 protein fell by 18 to 65%, with a parallel fall in its enzyme activity. Cell-associated glycosaminoglycans rose by 25 to 140%. Chondrocytes from 40% of patients did not respond to glucosamine.
This study measured MMP-3, a sister enzyme, not MMP13. The cells were in a dish with glucosamine added directly, and the abstract does not say how many patients donated cells or how long the cells were treated. The 40% non-response shows the effect was far from universal even in the lab. It does not tell us what concentration reaches cartilage after a person takes glucosamine by mouth.
Glucosamine is usually described as a building block. In these cells it worked on both sides, more aggrecan and less of a matrix-cutting enzyme, though the enzyme measured was MMP-3 rather than MMP13. That gap is why later studies that measured MMP13 directly matter.
The lab evidence is thin and mixed. Glucosamine lowered MMP13 in one study of human cartilage cells and stem cells, but in another it didn't change cytokine-driven...
It depends which part is damaged. Reviews describe losing aggrecan, the water-holding molecule in cartilage, as an early and reversible step, and losing type II collagen...