Cement penetration and stiffness of the cement-bone composite in the proximal tibia in a porcine model.

PURPOSE: To assess the stiffness of the cement bone composite and the depth and uniformity of cement penetration into the surface of the tibial component during total knee reconstruction in a porcine model. METHODS: The effectiveness of 3 protocols were compared: 2 commonly used cementing techniques-finger-packing of cement on the cut surface followed by impaction, and coating of the undersurface of the prosthesis with cement followed by impaction-and a new method using a tibial cement-pressurising device. Cement penetration was measured by computed tomography; stiffness was determined by hydraulic penetration testing. RESULTS: Cement penetration at a depth of 1 mm was significantly greater following coating the undersurface of the prosthesis than following finger-packing (p=0.008). There was no significant difference at deeper levels or between the tibial-pressurising device group and either of the 2 other groups at any level (p>0.3 in all cases). Differences in surface stiffness by tibial plateau region were found in tibiae that had been cemented using finger-packing and in those that had had their undersurface coated, but not in tibiae that had been cemented using the tibial-pressurising device. CONCLUSION: The tibial cement-pressurising device eliminated regional differences in stiffness seen with other cementing methods. Elimination of these differences by using this device should reduce micromotion and the incidence of aseptic loosening of tibial base plates in total knee arthroplasty.

PTHrP and cell division: expression and localization of PTHrP in a keratinocyte cell line (HaCaT) during the cell cycle.

Parathyroid hormone-related protein (PTHrP) is highly expressed in normal skin keratinocytes, and its involvement in growth and differentiation processes in these cells has been implicated by several lines of evidence which include the use of antisense PTHrP (Kaiser et al., 1994, Mol. Endocrinol., 8:139-147). In this study, we have investigated whether PTHrP expression and its subcellular localization is linked to cell cycle progression in a human keratinocyte cell line (HaCat), which constitutively expresses and secretes PTHrP. PTHrP mRNA and immunoreactive PTHrP were assessed in asynchronous dividing cells and in cells blocked at G1 or G2 + M phases of the cell cycle using several different protocols. The response of PTHrP mRNA expression was examined following readdition of serum in the continued presence of cycle blockers, and after release from cell cycle block, or from cell synchronization by serum deprivation. PTHrP expression was greatest in actively dividing cells when cells were in S and G2 + M phases of the cell cycle and were lowest in quiescent G1 cells. Most notable were the high levels of PTHrP mRNA and protein in cells at G2 + M phase of the cell cycle at division. Furthermore, PTHrP was localized to the nucleolus in quiescent cells, but redistributed to the cytoplasm when cells were actively dividing. Taken together, these results support a role for PTHrP in cell division in keratinocytes. In asynchronously growing cells, PTHrP expression fell as cells became confluent at a time when cell growth is inhibited and cells begin to differentiate. Mitogen stimulation of HaCaT cells resulted in a rapid increase in PTHrP mRNA expression, but was dependent upon cells being in the G1 phase of the cell cycle. Cells blocked in G1 responded to mitogen both in the continued presence of aphidicolin or when released from block. Cells blocked at G2 + M with colcemid expressed high levels of PTHrP mRNA and protein, and PTHrP mRNA did not respond further to mitogen in the continued presence of blocker. However, in cells released from block at G2 + M by addition of serum, an increase in PTHrP expression was seen coincident with the progression of cells into G1. In contrast, in a squamous cancer cell line (COLO16), basal PTHrP expression was high and was not altered during the cell cycle or by cell cycle block, consistent with association of its dysregulated expression in malignant cells. The results of this study suggest that PTHrP may have two roles in the cell cycle; one in G1 in response to mitogen, and a second at cell division when its expression is high and it is relocated from the nucleolus to the cytoplasm.