Based on our observations, we speculate that each tissue��s functional response is unique and the synchronization of individual physical and chemical properties could explain functional maintenance of the bone-PDL-cementum complex at an organ level. These changes can be related to functional loads, which act as stimuli to cells within various tissues and interfaces. Upon loading, molars pivot about the interradicular bone, which is considered as the natural fulcrum. Age-related changes in muscle efficiency and occlusion result in different chewing forces over time. As a result, functional loads alone can cause tension, compression, shear and related mechanical strains within the fibrous matrix between the bone and tooth. The effect of matrix-related strains, and fluid flow can be traced to changes in gene expressions of stem cells within the INCB18424 JAK inhibitor marrow space of the alveolar bone and blood vessels of the PDL. A good example is the origin of RANKL, a molecule involved in osteoclastogenesis, which can be traced from the vascularized PDL to bone marrow space containing stromal and hematopoietic stem cells. As a result, histomorphometric changes of load-bearing tissues with time included increased radial width of cementum and increased bone recession. Observed trends are reflective of bone ����carving,���� which would conceivably be due to functional adaptation and in turn could alter tooth attachment to bone to preserve optimal function space. Although age-related increases in cementum width and decreases in PDL-space were observed, the combined radial widths of SC and PDL-SC SCH772984 moa remained a constant in younger rats 1.5 to 6 months and in older rats 12 to 15 months. The functional role of SC and PDL in load adaptation provide the basis for considering the coupled PDL-cementum thickness in cooperative maintenance of the dynamic complex. Localized remodeling of bone is thought to dominate and allows for the uniform size increases in the growing periodontium between 1.5 to 4 months. When in function, modeling becomes more prevalent with complete secondary cementum formation and apposition from 4 to 15 months, simultaneously carving bone equivalent to tooth morphology as a result of functional stimuli. Changes in function can be identified as compromised PDL attachment and closing of endosteal spaces in rats 12 to 15 months of age. Generally, cement lines in bone increased, exhibiting a dominant lamellar-like pattern around endosteal and marrow spaces with age. The observed patterns can be associated with remodeling related events, which were identified in endocortical and marrow regions in aging rats. Based on narrowing endosteal spaces in aging rats, it is plausible that changes in PDL-width, bone and root surface are related to changes in blood flow, supply of nutrients, and chemotactic factors responsible for turnover of tissues.