Effects of Bisphosphonate on the Ossification of Growth Plate of the Knee Joint in Rats / 체질인류학회지

Bisphosphonates inhibit bone resorption by affecting osteoclastic function and formation of osteoclasts from their precursor cells. Chondroclasts have the same origin and differentiation as osteoclasts. Thus, it is hypothesized that bisphosphonate can affect on cartilage metabolism. This study was aimed to elucidate effects of alendronate, a nitrogen containing bisphosphonate, on cartilage development in the tibial proximal and femoral distal epiphyseal plates in rats. Alendronate (1 mg/kg) was subcutaneously administered in growing rat pups for 10 days. Several parameters such as the number and size of chondroclasts, involved in cartilage resorption, size of secondary ossification center and thickness of cartilage cell layers were measured and analysed by histomorphometry. The size of the secondary ossification centers in the tibial proximal and femoral distal epiphysis was smaller in the alendronate treated group (p 0.05). The thickness of proliferating cartilage layer was not changed, but by contrast, hypertrophied cartilage layer was increased in thickness by alendronate treatment. These findings suggest that bisphosphonates can affect cartilage cell metabolism in a chondroprotective way.

Immunohistochemical Study of Nitric Oxide Synthase in Pleomorphic Adenoma of the Salivary Glands / 대한해부학회지

Recent studies have suggested that nitric oxide (NO) exerts various effects on aspects of tumor biology, including angiogenesis and metastasis. There have been, however, scanty reports on nitric oxide synthase (NOS) response for tumors of the head and neck. This study was carried out to assess the distribution of both endothelial NOS (eNOS) and inducible NOS (iNOS) in normal salivary gland tissue and in pleomorphic adenoma by using immunohistochemistry. In the present study, eNOS and iNOS were higher expressed in pleomorphic adenoma than adjacent normal salivary gland tissue, suggesting that up-regulation of this enzyme is associated with tumor progression. Additionally, eNOS and iNOS expression were higher in epithelial components than in mesenchymal components. Overall, iNOS expression was higher than eNOS expression in pleomorphic adenoma. In normal tissues adjacent to pleomorphic adenoma, iNOS expression was higher in the mesenchymal type than in the epithelial type of pleomorphic adenoma. It is suggested that NO may play a role in the tumorgenesis and propagation of pleomorphic adenoma.

Regulation of Osteoclasts via Osteoblasts by Alendronate / 대한해부학회지

Bisphosphonates have been used for the prevention of pathological bone resorption and its related disease for their high affinity to hydroxyapatite and direct effects on osteoclasts. Several studies have shown that in vitro the potency of bisphosphonates for osteoclasts is not coincident with in vivo results, which proposes other mechanisms may be involved in their inhibition of bone resorption. Osteoblasts have paracrine regulation for osteoclast activities and formation. Thus, it is hypothesized that bisphosphonates may have indirect effects on osteoblasts to regulate osteoclastic bone resorption. This study was carried out to investigate molecular mechanism that alendronate, a nitrogen containing bisphosphponate, acts on osteoblasts to regulate osteoclastic bone resorption in vivo and in vitro system. In vitro MTS system using MC3T3-E1 osteoblastic cell line, absorbance values increased at 10(-10) to 10(-4) M concentration after a day treatment of alendronate. The values decreased at 3 and 5 days after treatment at 10(-5) M higher concentration. Gene expression levels of ALP, OPG and type I collagen were not changed at both 10(-5) M and 10(-6) M. However, MCP-1 and M-CSF notably decreased in their gene expression by the treatment. In vivo system using the rat pup tibia, M-CSF gene expression decreased a lot by alendronate treatment. The number of osteoclasts significantly decreased from trabeculae of femur and tibia in alendronate treated group (p < 0.01). Furthermore, trabeculae themselves underneath the epiphyseal plate were longer in the alendronate treated group (p< 0.01). These results suggested that bisphosphonates can indirectly inhibit osteoclastic bone resorption by affecting osteoblasts to regulate osteoclasts at molecular level.

Regeneration of Artificial Bone Defects by Allograft of Demineralized Bone and Bone Particles in Rabbits / 대한해부학회지

Since bone matrix is known to contain osteoinductive substance, many studies have been carried out for its clinical applications. But there are still controversies about its regeneration effects and bone induction. This study was performed to compare the bone induction and regeneration between bone matrix particles (BMP) and demineralized bone matrix particles (DMP). About 700 mm BMP and DMP were made from long bone of adult rabbit. They were allografted into the artificial defect formed at medial surface of tibia and observed using LM and fluorescent microscopy. More fibrin networks and osteoblasts were formed in the graft groups than in control group after 3 days of graft. At one week after graft active endochondral and intramembranous ossification were taking place by osteoinduction around the DMP, whereas osteoinduction is rarely seen around the BMP. Most of regenerated trabecular bone was replaced by immature lamellar bone in DMP group, while some amount of fibrous and trabecular structures still remained in the defect in BMP group at 4 weeks after graft. More rapid bone regeneration and maturity were seen in DMP grafted group than in BMP grafted and control groups in fluorescent microscopy at each week after graft. These results suggest that demineralized bone matrix graft is more effective than that of mineralized bone matrix in regeneration of bone defect and endochondral bone formation is not necessary in osteoinduction.