Diabetes Causes Decreased Osteoclastogenesis, Reduced Bone Formation, and Enhanced Apoptosis of Osteoblastic Cells in Bacteria Stimulated Bone Loss

Abstract

The most common cause of inflammatory bone loss is periodontal disease. After bacterial insult, inflammation induces bone resorption, which is followed by new reparative bone formation. Because diabetics have a higher incidence and more severe periodontitis, we examined mechanisms by which diabetes alters the response of bone to bacterial challenge. This was accomplished with db/db mice, which naturally develop type 2 diabetes. After inoculation of bacteria osteoclastogenesis and bone resorption was measured. Both parameters were decreased in the diabetic group. Diabetes also suppressed reparative bone formation measured histologically and by the expression of osteocalcin. The impact of diabetes on new bone formation coincided with the effect of diabetes on apoptosis of bone-lining cells. Within 5 d of bacterial challenge, apoptosis declined in the wild-type animals yet remained significantly higher in the diabetic group. Thus, diabetes may cause a net loss of bone because the suppression of bone formation is greater than the suppression of bone resorption. The uncoupling of bone formation and resorption may be due in part to prolonged apoptosis of bone lining cells.

Effects on Alveolar Bone of Diabetes Mellitus Induced by Streptozotocin in Rats. Histopathologic and Immunohistochemical Study

“…The worsening of alveolar bone loss observed in diabetic animals with periodontal disease supporting previous studies, since there is a bidirectional relationship between these diseases (Breivik et al, 2005;Kim et al, 2012). In a research C57BL Db/db mice that developed diabetes at six to eight weeks of age to study decreased osteoclastogenesis in bacteria-stimulated bone loss (He et al, 2004). Jiang et al (2013) reported resorption values of alveolar bone in the upper second molar of four groups of rats at different time points.…”

Alloxan-induced diabetes delays repair in a rat model of closed tibial fracture

“…Figure 3. www.bjournal.com.br bone, as reported in other diabetes models (6)(7)(8)(9)(10)(11)(12)(21)(22)(23)(24).…”

“…These include reduction in blood supply and angiogenesis (1), a more severe inflammatory response (18,19), a decrease in collagen synthesis (6,20,21), a disturbance in the mineralization process (9,11,12), and an imbalance between bone resorption by osteoclasts and bone deposition by osteoblasts (22)(23)(24). Another contributing factor may be the advanced glycation end products, present in high levels in diabetic individuals, that amplify inflammatory events (25) and delay wound healing (26).…”

Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways

“…To test whether AGEs stimulated apoptosis of bone-lining cells in vivo, CML-collagen and control collagen were injected adjacent to the scalp periosteum and apoptosis of periosteal cells was measured by the TUNEL assay as we have previously described (16). CML-collagen stimulated a 5 fold increase in apoptosis of these bone lining cells compared to unmodified collagen (Fig.…”

“…For example, premature aging caused by ablation of the klotho gene is associated with higher levels of osteoblast and osteocyte apoptosis (45). We have recently shown that diabetes causes enhanced apoptosis of osteoblastic cells following a bacterial stimulus (16). When apoptosis is inhibited there is a significant improvement in the capacity to form new bone demonstrating that diabetes-enhanced apoptosis is functionally important (5).…”