Histologic evaluation of root response to intrusion in mandibular teeth in beagle dogs

Authors

Juan I. Ramirez-Echave, Peter H. Buschang, Roberto Carrillo, P. Emile Rossouw, William W. Nagy, Lynne A. Opperman

Abstract

The purpose of this article was to histologically evaluate root resorption and repair after orthodontic intrusion with different force magnitudes and fixed anchorage. A randomized split-mouth repeated-measure design was used. Intrusive forces were applied for 98 days to the mandibular second, third, and fourth premolars of 8 mature beagle dogs. Two miniscrew implants were used as anchorage to apply constant intrusive forces of 50, 100, or 200 g per tooth. Demineralized sections of each tooth were stained and histologically studied for root resorption. Multilevel statistical procedures were used to evaluate the results. Root resorption was present in all teeth, independent of the force applied. Significant differences were found between root regions, with the apices and the interradicular regions the most affected and with dentin involvement at the furcation. There was cementum repair in 24.14% of the lacunae. Light constant intrusive forces between 50 and 200 g showed no significant differences in the amount of resorption produced. Resorption was more frequently seen at the level of the apices and the furcation. Orthodontically induced root resorption is not clinically significant after application of continuous intrusive forces between 50 and 200 g. Moreover, there is no relationship between root resorption, the position of posterior mandibular teeth in the arch, and the amount of intrusive force applied.

Link to Article

http://dx.doi.org/10.1016/j.ajodo.2009.07.014

Skeletal effects of whole-body vibration in adult and aged mice

Authors

Michelle A. Lynch, Michael D. Brodt, Matthew J. Silva

Abstract

Low-amplitude, whole-body vibration (WBV) may be anabolic for bone. Animal studies of WBV have not evaluated skeletal effects in aged animals. We exposed 75 male BALB/c mice (7 month/young-adult; 22 month/aged) to 5 weeks of daily WBV (15 min/day, 5 day/wk; 90 Hz sine wave) at acceleration amplitudes of 0 (sham), 0.3, or 1.0 g. Whole-body bone mineral content (BMC) increased with time in 7 month (p < 0.001) but not 22 month (p = 0.34) mice, independent of WBV (p = 0.60). In 7 month mice, lower-leg BMC increased with time in 0.3 and 1.0 g groups (p < 0.005) but not in the sham group (p = 0.09), indicating a positive WBV effect. In 22 month mice, there were no changes with time in lower-leg BMC (p = 0.11). WBV did not affect tibial trabecular or cortical bone structure (by µCT), dynamic indices of trabecular or cortical bone formation, trabecular osteoclast surface, or the mass of the reproductive fat pad (p > 0.05). Each of these outcomes was diminished in 7 month versus 22 month animals (p < 0.05). In summary, 5 weeks of daily exposure to low-amplitude WBV had no skeletal effects in aged male mice. The potential of WBV to enhance bone mass in age-related osteoporosis is not supported in this preclinical study.

Link to Article

http://dx.doi.org/10.1002/jor.20965

Suberoylanilide hydroxamic acid (SAHA; vorinostat) causes bone loss by inhibiting immature osteoblasts

Authors

Meghan E. McGee-Lawrence and Angela L. McCleary-Wheeler and Frank J. Secreto and David F. Razidlo and Minzhi Zhang and Bridget A. Stensgard and Xiaodong Li and Gary S. Stein and Jane B. Lian and Jennifer J. Westendorf

Abstract

Histone deacetylase (Hdac) inhibitors are used clinically to treat cancer and epilepsy. Although Hdac inhibition accelerates osteoblast maturation and suppresses osteoclast maturation in vitro, the effects of Hdac inhibitors on the skeleton are not understood. The purpose of this study was to determine how the pan-Hdac inhibitor, suberoylanilide hydroxamic acid (SAHA; a.k.a. vorinostat or ZolinzaTM) affects bone mass and remodeling in vivo. Male C57BL/6 mice received daily SAHA (100 mg/kg) or vehicle injections for 3 to 4 weeks. SAHA decreased trabecular bone volume fraction and trabecular number in the distal femur. Cortical bone at the femoral midshaft was not affected. SAHA reduced serum levels of P1NP, a bone formation marker, and also suppressed tibial mRNA levels of type I collagen, osteocalcin and osteopontin, but did not alter Runx2 or osterix transcripts. SAHA decreased histological measures of osteoblast number but interestingly increased indices of osteoblast activity including mineral apposition rate and bone formation rate. Neither serum (TRAcP 5b) nor histological markers of bone resorption were affected by SAHA. P1NP levels returned to baseline in animals which were allowed to recover for 4 weeks after 4 weeks of daily SAHA injections, but bone density remained low. In vitro, SAHA suppressed osteogenic colony formation, decreased osteoblastic gene expression, induced cell cycle arrest, and caused DNA damage in bone marrow-derived adherent cells. Collectively, these data demonstrate that bone loss following treatment with SAHA is primarily due to a reduction in osteoblast number. Moreover, these decreases in osteoblast number can be attributed to the deleterious effects of SAHA on immature osteoblasts, even while mature osteoblasts are resistant to the harmful effects and demonstrate increased activity in vivo, indicating that the response of osteoblasts to SAHA is dependent upon their differentiation state. These studies suggest that clinical use of SAHA and other Hdac inhibitors to treat cancer, epilepsy or other conditions may potentially compromise skeletal structure and function.

Link to Article

http://dx.doi.org/10.1016/j.bone.2011.01.007

Analysis of osteoarthritis in a mouse model of the progeroid human DNA repair syndrome trichothiodystrophy

Authors

Sander M. Botter, Michel Zar, Gerjo J. V. M van Osch, Harry van Steeg, Martijn E. T. Dollé, Jan H. J. Hoeijmakers, Harrie Weinans and Johannes P. T. M. van Leeuwen

Abstract

The increasing average age in developed societies is paralleled by an increase in the prevalence of many age-related diseases such as osteoarthritis (OA), which is characterized by deformation of the joint due to cartilage damage and increased turnover of subchondral bone. Consequently, deficiency in DNA repair, often associated with premature aging, may lead to increased pathology of these two tissues. To examine this possibility, we analyzed the bone and cartilage phenotype of male and female knee joints derived from 52- to 104-week-old WT C57Bl/6 and trichothiodystrophy (TTD) mice, who carry a defect in the nucleotide excision repair pathway and display many features of premature aging. Using micro-CT, we found bone loss in all groups of 104-week-old compared to 52-week-old mice. Cartilage damage was mild to moderate in all mice. Surprisingly, female TTD mice had less cartilage damage, proteoglycan depletion, and osteophytosis compared to WT controls. OA severity in males did not significantly differ between genotypes, although TTD males had less osteophytosis. These results indicate that in premature aging TTD mice age-related changes in cartilage were not more severe compared to WT mice, in striking contrast with bone and many other tissues. This segmental aging character may be explained by a difference in vasculature and thereby oxygen load in cartilage and bone. Alternatively, a difference in impact of an anti-aging response, previously found to be triggered by accumulation of DNA damage, might help explain why female mice were protected from cartilage damage. These findings underline the exceptional segmental nature of progeroid conditions and provide an explanation for pro- and anti-aging features occurring in the same individual. 

Link to Article

http://dx.doi.org/10.1007/s11357-010-9175-3

Temporal and spatial expression of osteoactivin during fracture repair

Authors

Samir M. Abdelmagid, Mary F. Barbe, Michael Hadjiargyrou, Thomas A. Owen, Roshanak Razmpour, Saqib Rehman, Steven N. Popoff, Fayez F. Safadi

Abstract

We previously identified osteoactivin (OA) as a novel secreted osteogenic factor with high expression in developing long bones and calvaria, and that stimulates osteoblast differentiation and matrix mineralization in vitro. In this study, we report on OA mRNA and protein expression in intact long bone and growth plate, and in fracture calluses collected at several time points up to 21 days post-fracture (PF). OA mRNA and protein were highly expressed in osteoblasts localized in the metaphysis of intact tibia, and in hypertrophic chondrocytes localized in growth plate, findings assessed by in situ hybridization and immunohistochemistry, respectively. Using a rat fracture model, Northern blot analysis showed that expression of OA mRNA was significantly higher in day-3 and day-10 PF calluses than in intact rat femurs. Using in situ hybridization, we examined OA mRNA expression during fracture healing and found that OA was temporally regulated, with positive signals seen as early as day-3 PF, reaching a maximal intensity at day-10 PF, and finally declining at day-21 PF. At day-5 PF, which correlates with chondrogenesis, OA mRNA levels were significantly higher in the soft callus than in intact femurs. Similarly, we detected high OA protein immuno-expression throughout the reparative phase of the hard callus compared to intact femurs. Interestingly, the secreted OA protein was also detected within the newly made cartilage matrix and osteoid tissue. Taken together, these results suggest the possibility that OA plays an important role in bone formation and serves as a positive regulator of fracture healing.

Link to Article

http://dx.doi.org/10.1002/jcb.22702