The C-Terminal Intact Forms of Periostin (iPTN) Are Surrogate Markers for Osteolytic Lesions in Experimental Breast Cancer Bone Metastasis.

Periostin is an extracellular matrix protein that actively contributes to tumor progression and metastasis. Here, we hypothesized that it could be a marker of bone metastasis formation. To address this question, we used two polyclonal antibodies directed against the whole molecule or its C-terminal domain to explore the expression of intact and truncated forms of periostin in the serum and tissues (lung, heart, bone) of wild-type and periostin-deficient mice. In normal bones, periostin was expressed in the periosteum and specific periostin proteolytic fragments were found in bones, but not in soft tissues. In animals bearing osteolytic lesions caused by 4T1 cells, C-terminal intact periostin (iPTN) expression disappeared at the invasive front of skeletal tumors where bone-resorbing osteoclasts were present. In vitro, we found that periostin was a substrate for osteoclast-derived cathepsin K, generating proteolytic fragments that were not recognized by anti-periostin antibodies directed against iPTN. In vivo, using an in-house sandwich immunoassay aimed at detecting iPTN only, we observed a noticeable reduction of serum periostin levels (- 26%; P < 0.002) in animals bearing osteolytic lesions caused by 4T1 cells. On the contrary, this decrease was not observed in women with breast cancer and bone metastases when periostin was measured with a human assay detecting total periostin. Collectively, these data showed that mouse periostin was degraded at the bone metastatic sites, potentially by cathepsin K, and that the specific measurement of iPTN in serum should assist in detecting bone metastasis formation in breast cancer.

The in vitro effect of different implant angulations and cyclic dislodgement on the retentive properties of an overdenture attachment system.

STATEMENT OF PROBLEM: The retentive capacity of ball attachments may be altered by a change in implant angulations. PURPOSE: The purpose of this in vitro study was to investigate the effect of cyclic dislodgement on the retention of an overdenture attachment system when 2 implants were placed at angulations of 0, 5, 10, 15, and 20 degrees. MATERIAL AND METHODS: Twelve acrylic resin blocks were fabricated and divided into 6 groups of 2 pairs each. In each of the 6 groups, 1 acrylic resin block was used to house the implants (block A), while the other (block B) was used to house the overdenture attachments. Two implants positioned at 0/0 degrees, with a standard plastic component(white) designed for 0-degree angulations, served as a control (CTRL), while the other 5 pairs of implants were placed in 5 different angulations: 0D: 0/0 degrees, 5D: 5/5 degrees, 10D: 10/10 degrees, 15D: 15/15 degrees, 20D: 20/20degrees (n=5). The extended range (green color) attachment was used for all groups except the control group. Implants(4.3 mm x 13 mm, internally hexed) were placed in blocks B. All angled implants were mesially tilted. Thirty pairs of attachments (Locator) were used. Dislodging cycles were applied to the overdenture attachment system. The initial retentive forces among the groups were not identical. The cycles required for the retentive forces of the attachments to decrease from the initial values to 60 N, and then to 40 N and 20 N, were recorded for standardization purposes.One-way ANOVA and Tukey HSD tests were used to analyze the difference in retention loss among the 6 groups(alpha=.05). A regression analysis (alpha=.05) was also performed to investigate the relationship between the implant angulation,the retentive force, and the logarithm of the number of cycles required for ball attachment retention decrease. RESULTS: The 1-way ANOVA and the Tukey HSD tests revealed significant differences for the number of cycles required by different implant angulation groups for the initial retentive values to decrease to 60 N, 40 N, and 20 N (P<.001).The 0D and 5D groups required the longest time for retention loss, while 20D and CTRL groups demonstrated the shortest time for retention loss. The results of the regression analysis of the logarithmic number of cycles on retentive force and implant angulation demonstrated a significant effect (P<.001). CONCLUSIONS: Implant angulations negatively affect attachment retention longevity. (J Prosthet Dent 2009;102:140-147)