OSTEOGENIC INHIBITION BY RAT PERIODONTAL-LIGAMENT CELLS - MODULATION OF BONE MORPHOGENIC PROTEIN-7 ACTIVITY IN-VIVO

Periodontal ligament width is precisely maintained throughout the life time of adult mammals but the biological mechanisms that inhibit ingro wth of bone into this soft connective tissue are unknown. As bone morp hogenic proteins strongly stimulate osteogenesis and can induce ectopi c bone formation in vivo, we tested the hypothesis that topical applic ation of this powerful osteogenic agent will overwhelm the osteogenic inhibitory mechanisms of periodontal ligament cells and induce ankylos is. Wounds through the alveolar bone and periodontal ligament were cre ated in 45 male Wistar rats. Defects were filled with either a collage n implant or collagen plus bone morphogenic protein (BMP-7), or were l eft unfilled (controls). Three animals per time period were killed on days 2, 5, 10, 21 and 60 after surgery for each wound type. Cellular p roliferation and clonal growth in periodontal tissues were assessed by H-3-thymidine labeling 1 h before death, followed by radioautography. Cellular differentiation of soft and mineralizing connective tissue c ell populations was determined by immunohistochemical staining of a-sm ooth muscle actin, osteopontin and bone sialoprotein. In regenerating periodontium, BMP-7 induced abundant bone formation by 21 days (2.5-fo ld greater than controls or collagen implant only; P<0.001), but by da y 60 the volume of the newly formed bone had returned to baseline leve ls and was similar for all groups. Independent of the type of treatmen t, periodontal ligament width was unchanged throughout the experimenta l period (P>0.05). Animals treated with BMP-7 implants showed greatly increased cellular proliferation in the periodontal ligament adjacent to the wound site and in the regenerating alveolar bone at days 5 and 10 after wounding compared to the other treatment groups (P<0.005). An imals in the BMP-7 group exhibited similar spatial and temporal staini ng patterns for a-smooth muscle actin, osteopontin and bone sialoprote in as controls. Collectively, these data show that BMP-7 promoted the proliferation of precursor cells in the periodontal ligament but did n ot induce osteogenic differentiation in this compartment. Consequently a powerful osteogenic stimulus like BMP-7 cannot significantly pertur b the mechanisms that regulate periodontal ligament width and maintain periodontal homeostasis.