Enhanced trabecular bone resorption and microstructural bone changes in rats after removal of the cecum

Item does not contain fulltextThe cecum, the proximal part of the large intestine, has the highest rate of calcium absorption compared with other intestinal segments. Previously, we showed that rats with the cecum surgically removed (cecectomized rats) had severe negative calcium balance, low bone mineral density (BMD), and a compensatory increase in colonic calcium absorption. Herein, we used the computer-assisted bone histomorphometric technique and microcomputed tomography (muCT) to analyze bone microstructural defects in cecectomized rats at 1 and 3 mo postsurgery compared with age-matched sham-operated control rats. Relatively low BMD as determined by dual energy X-ray absorptiometry was observed in the femora, tibiae, and lumbar vertebrae of the 3-mo cecectomized rats. muCT analysis revealed decreases in the tibial cortical thickness, periosteal and endosteal perimeters, and moment of inertia in cecectomized rats. The histomorphometric results further showed that trabecular bone volume and number were markedly decreased, whereas trabecular separation was increased in the proximal tibial metaphysis of cecectomized rats, thus leading to a decrease in trabecular volumetric BMD. Since osteoclast surface and eroded surface were increased after cecectomy, such bone loss in cecectomized rats appeared to result from an enhanced bone resorption. Moreover, decreases in bone formation rate and osteoblast surface indicated a suppression of osteoblast-mediated bone formation. In conclusion, cecectomy induced widespread osteopenia in rats presumably by enhancing the osteoclast-mediated bone resorption and suppressing bone formation. The present results underline the important role of cecum in the body calcium homeostasis

Impaired body calcium metabolism with low bone density and compensatory colonic calcium absorption in cecectomized rats

Item does not contain fulltextAn earlier study reported that cecal calcium absorption contributes less than 10% of total calcium absorbed by the intestine, although the cecum has the highest calcium transport rate compared with other intestinal segments. Thus, the physiological significance of the cecum pertaining to body calcium metabolism remains elusive. Herein, a 4-wk calcium balance study in cecectomized rats revealed an increase in fecal calcium loss with marked decreases in fractional calcium absorption and urinary calcium excretion only in the early days post-operation, suggesting the presence of a compensatory mechanism to minimize intestinal calcium wasting. Further investigation in cecectomized rats showed that active calcium transport was enhanced in the proximal colon but not in the small intestine, whereas passive calcium transport along the whole intestine was unaltered. Since apical exposure to calcium-sensing receptor (CaSR) agonists similarly increased proximal colonic calcium transport, activation of apical CaSR in colonic epithelial cells could have been involved in this hyperabsorption. Calcium transporter genes, i.e., TRPV6 and calbindin-D(9k), were also upregulated in proximal colonic epithelial cells. Surprisingly, elevated serum parathyroid hormone levels and hyperphosphatemia were evident in cecectomized rats despite normal plasma calcium levels, suggesting that colonic compensation alone might be insufficient to maintain normocalcemia. Thus, massive bone loss occurred in both cortical and trabecular sites, including lumbar vertebrae, femora, and tibiae. The presence of compensatory colonic calcium hyperabsorption with pervasive osteopenia in cecectomized rats therefore corroborates that the cecum is extremely crucial for body calcium homeostasis

Thrombin receptor deficiency leads to a high bone mass phenotype by decreasing the RANKL/OPG ratio

Thrombin and its receptor (TR) are, respectively, expressed in osteoclasts and osteoblasts. However, their physiological roles on bone metabolism have not been fully elucidated. Here we investigated the bone microarchitecture by micro-computed tomography (μCT) and demonstrated increased trabecular and cortical bone mass in femurs of TR KO mice compared to WT littermates. Trabecular thickness and connectivity were significantly enhanced. The physiological role of TR on both inorganic and organic phases of bone is illustrated by a significant increase in BMD and a decrease in urinary deoxypyridinoline (DPD) crosslink concentration in TR KO mice. Moreover, TR KO cortical bone expanded and had a higher polar moment of inertia (J), implying stronger bone. Bone histomorphometry illustrated unaltered osteoblast and osteoclast number and surface in femoral metaphyses, indicating that thrombin/TR regulates osteoblasts and osteoclasts at functional levels. Serum analysis showed a decrease in RANKL and an increase in osteoprotegerin (OPG) levels and reflected a reduced RANKL/OPG ratio in the TR KO group. In vitro experiments using MC3T3 pre-osteoblasts demonstrated a TR-dependent stimulatory effect of thrombin on the RANKL/OPG ratio. This effect was blocked by TR antagonist and p42/p44-ERK inhibitor. In addition, thrombin also intensified p42/p44-ERK expression and phosphorylation. In conclusion, the thrombin/TR system maintains normal bone remodeling by activating RANKL and limiting OPG synthesis by osteoblasts through the p42/44-ERK signaling pathway. Consequently, TR deficiency inhibits osteoclastogenesis, resulting in a high bone mass phenotyp

Leptospira pre-protein translocase (secY) gene, partial cds.

Leptospira infection and shedding in dogs in Thailan

Leptospira pre-protein translocase (secY) gene, partial cds.

Leptospira infection and shedding in dogs in Thailan