Increased expression of matrix metalloproteinase-1 in osteocytes precedes bone resorption as stimulated by disuse: Evidence for autoregulation of thecell's mechanical environment?

An in vivo animal model of bone adaptation was used to examine a possible r ole for matrix metalloproteinase-l in the local mediation of bone remodelin g: to corrode, the coupling of osteocytes to the matrix in an attempt to au toregulate the cell's perception of its mechanical environment. Twelve youn g (12-16 months old) skeletally mature turkeys were separated into groups t o be studied for stimulus periods of either 3 or 30 days. In each animal, t he left ulna was functionally isolated and subjected to either disuse or 3, 000 microstrain at 1 Hz for 10 minutes per day. The right ulna remained int act and served as an intra-animal control. No significant differences in bo ne area were detected at 3 days; however, ulnae subjected to disuse lost 8 +/-. 4% (SD) of bone area by 30 days. Over the same period, ulnae subjected to the mechanical stimulus gained 21 +/- 9% of bone area. With use of in s itu reverse transcription-polymerase chain reaction, less than 2% of the os teocytes examined from the intact control ulnae stained positively for matr ix metalloproteinase-l mRNA. An antibody raised against matrix metalloprote inase-l revealed no:positively labeled osteocytes in the intact ulnae. This low percentage of osteocytes expressing matrix metalloproteinase-l mRNA wa s similar to that seen in ulnae subjected to the osteogenic mechanical stim uli. In contrast, ulnae subjected to either 3 or 30 days of disuse showed e vidence of matrix metalloproteinase-l mRNA activity in a high percentage of osteocytes (89 +/- 5 and 66 +/- 8%, respectively; each time point signific antly different from intact ulnae, as well as from each other, p < 0.05). T he percentage of osteocytes labeled with the anti-matrix metalloproteinase- l antibody was also highly elevated following 3 days of disuse (74 +/- 17%) . These data demonstrate that an early response of bone to disuse is the up regulation of matrix metalloproteinase-l activity in osteocytes. It is prop osed that this upregulation of collagenase,activity is indicative of the ce ll's degradation of coupling to the matrix, and it thus reflects the osteoc yte's regulation of,its own mechanical environment. We believe that such au toregulation of the osteocyte's physical environment will accommodate subtl e changes in the bone's functional environment without the need to add or r esorb bone tissue.