Transport of nutrients, cytokines, pharmacologic agents, and matrix co
mponents through articular cartilage is critical for the viability and
structural integrity of the tissue. To understand the role of the ext
racellular matrix in regulating this process, we measured the diffusiv
ity of three uncharged solutes of different molecular size (glucose, M
W 180; inulin, MW 5000; dextran, MW 70,000) into intact cartilage and
cartilage that had its proteoglycan (PG) component removed. Solute dif
fusivity was measured by performing transient (nonsteady state) one-di
mensional diffusion tests using radiolabelled solutes. Compared to int
act cartilage, the diffusivity of glucose was unchanged after PG remov
al, inulin was unchanged but dextran increased by 1.7 times after 71%
PG removal, and both inulin and dextran increased by 1.6 and 2.0 times
, respectively, after 93% PG removal. The diffusivities of inulin and
dextran were inversely proportional to the PG content. While no change
was found in the tissue's bulk fluid content, PG depletion resulted i
n an increase in fluid content in the upper regions of the tissue and
a decrease in the lower regions. These results indicate that in intact
tissue small uncharged solutes have free mobility through the inter-m
olecular and intra-molecular PG volumes, larger molecules have limited
intra-molecular mobility, and very large molecules are excluded from
the intra-molecular space. (C) 1997 Elsevier Science Ltd.