Articular cartilage is known to be responsive to mechanical stimuli. Since the pioneering studies of Ken Brandt's group, in which they showed that remobilized joints regained proteoglycan lost during immobilization (1;2), there have been many in vivo and in vitro studies in which mechanical loads have been applied to cartilage. Like many others, we found that cyclic loads of approximately walking frequency and magnitude stimulated matrix formation whereas static loads of the same magnitude inhibited matrix biosynthesis (3). Most of this work, however, has been done on animal tissue. This is easier to obtain and ostensibly appears very similar to human cartilage. There were some hints, however, from studies by Alice Maroudas' group that human cartilage might not behave in the same way (4), but this seemed largely to have been overlooked. A little strange, given that most researchers are interested primarily in human physiology and OA in humans is the main disease to which the results are related. We have begun to investigate further the effects of cyclic and static loads in biopsies of human articular cartilage obtained from the femoral head of patients undergoing surgery for a fractured neck of femur (5;6). The cartilage obtained from these, mainly elderly, patients is often in surprisingly good condition with no evidence of fibrillation.
Full depth cartilage biopsies of articular cartilage were removed from defined sites on femoral heads. These explants were subjected to either static or cyclic (2 seconds on/2 seconds off) loading in unconfined compression at a stress of 1 MPa for 24 hours, or were left unloaded to act as a control. Metabolic activity was assessed by metabolic labelling during the last 4 hours of loading and measuring the incorporated radioisotopes. Matrix composition was also measured in terms of the amounts of collagen, sulphated glycosaminoglycans (GAG) and water content. Both cyclic and static loading reduced the incorporation into the tissue of 35 S-sulphate and 3 H-leucine, though cyclic not as much as static. Addition of IGF-1 was found to stimulate isotope incorporation, by 80% for 35 S-SO 4 and 40% for 3 H-leucine. If loads, either cyclic or static, were then applied in the presence of IGF-1, these returned the incorporation rates to their unstimulated levels. This study suggests elderly human articular cartilage is responsive to stimulation by IGF-1 but mechanical factors seem to act sufficiently strongly in the opposite direction to cancel this response. Without IGF-1, they inhibit matrix formation. These results are in contrast to previous studies on young bovine tissue where cyclic loading is stimulatory and is reported to act additively with IGF-1 (7) . There are two factors that could underly the differences between this and previous studies: the first is the age of the tissue and the other is a species difference. Unravelling this will not be easy as it is very difficult to obtain either young human tissue or elderly bovine. It does indicate, though, that extrapolating results from studies on animals to humans needs to be done with care.
References
(1) Palmoski MJ, Perricone E, Brandt KD. Development and reversal of a proteoglycan aggregation defect in normal canine knee cartilage after immobilization. Arthritis Rheum 22 : 508-517, 1979.
(2) Palmoski MJ, Colyer RA, Brandt KD. Joint motion in the absence of normal loading does not maintain normal articular cartilage. Arthritis Rheum 23 : 325-334, 1980.
(3) Larsson T, Aspden RM, Heinegård D. Effects of mechanical load on cartilage matrix biosynthesis in vitro. Matrix 11 : 388-394, 1991.
(4) Schneiderman R, Keret D, Maroudas A. Effects of mechanical and osmotic pressure on the rate of glycosaminoglycan synthesis in the human adult femoral head cartilage: an in vitro study. J Orthop Res 4 : 393-408, 1986.
(5) Plumb MS, Aspden RM. The response of elderly human articular cartilage to mechanical stimuli in vitro. Osteoarthritis Cart 13 : 1084-1091, 2005.
 
(6) Plumb MS, Treon K, Aspden RM. Competing regulation of matrix biosynthesis by mechanical and IGF-1 signalling in elderly human articular cartilage in vitro. Biochim Biophys Acta 1760 : 762-767, 2006.
(7) Bonassar LJ, Grodzinsky AJ, Frank EH, Davila SG, Bhaktav NR, Trippel SB. The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-I. J Orthop Res 19 : 11-17, 2001. |
