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Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 209 - 209
1 Jul 2014
MCP-1 IN THE PERIOSTEUM AND THE ENDOSTEUM AT THE EARLY INFLAMMATORY PHASE IS AN ESSENTIAL COMPONENT FOR SUCCESSFUL FRACTURE HEALING
Ishikawa M Ito H Yoshitomi H Murata K Shibuya H Furu M Kitaori T Nakamura T Matsuda S
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Summary Statement

MCP-1/ CCR2 axis at the early phase plays a pivotal role in the fracture healing. Inflammation plays a pivotal role in fracture healing. Among them, chemokines play key roles in inflammation. Monocyte chemotactic protein-1 (MCP-1), via its receptor C-C chemokine receptor 2 (CCR2), acts as a potent chemoattractant for various cells to promote migration from circulation to inflammation site. Thus, the importance of MCP-1/CCR2 axis in fracture healing has been suggested. However, the involvement of MCP-1/CCR2 axis tofracture site is not fully elucidated.

Results

PCR Array: The expression of MCP-1 and MCP-3 had increased on day 2 than 0 or 7 in the rib fracture healing. Immunohistochemistry Staining: To verify the localization of MCP-1 expression, we examined the Wild type (WT)-mouse rib fracture healing. We observed high expression of MCP-1 and MCP-3 at the periosteum and the endosteum on post-fracture day 3. In vivo Antagonist Study: To elucidate whether MCP-1/CCR2 axis is involved during the early phase of fracture healing, we continuously administered RS102895, CCR2 antagonist, before or after rib fracture. Micro-CT analysis showed delayed fracture healing in the before-group compared with both the control and after-group. On day 21, the hard callus volume in the before-group was significantly smaller than that in the control-group. Histological analysis showed that fractures in both the control and the after-groups were healed by day 21. In contrast, less of cartilage in the callus was observed in the before-group on day 7. Gain of Function: To examine the roles of MCP-1 at the periosteum and the endosteum during the fracture healing, we created a segmental bone graft exchanging model. The bone grafts were transplanted from MCP-1−/− mice to another MCP-1−/− mice (KO-to-KO). Micro-CT analysis showed that KO-to-KO transplantation led to the delay of fracture healing on day 21. Next, we created exchanging-bone graft models between MCP-1−/− and WT mice, in which a segmental bone derived from a WT mouse was transplanted into a host MCP-1−/− mouse (WT-to-KO). In contrast to KO-to-KO bone graft transplantation, the transplantation of WT-derived graft into host KO mouse resulted in a significant increase of new bone formation on day 21. Histological analysis revealed that marked and localised induction of MCP-1 expression in the periosteum and the endosteum around the WT-derived graft was observed in the host MCP-1−/− mouse. Loss of Function: To validate whether MCP-1 is a crucial chemokine for fracture healing, we created WT-to-WT and KO-to-WT bone graft models. When WT-donor graft was transplanted into WT-host, abundant new bone formation was observed around a WT-derived graft on day 21. In contrast, transplantation of KO-derived graft into WT-host resulted in a marked reduction of periosteal bone formation on a donor graft.

Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 405 - 405
1 Nov 2011
A727. LONG TERM DURABILITY IN DEEP FLEXION KNEE WITH BI-SURFACE KNEE ARTHROPLASTY
Nakamura S Kobayashi M Ito H Yoshitomi H Arai R Nakamura K Ueo T Nakamura T
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In Far East, including Japan and the Middle East, daily activities are frequently carried out on the floor. Deep flexion of the knee joint is therefore very important in these societies. Some patients who underwent total knee arthroplasty (TKA) in these countries often perform deep flexion activity, such as squatting, cross-leg sitting and kneeling. However it is still unknown that deep flexion activity affects long term durability after TKA. The purpose of this study was to examine the correlation between deep flexion and long term durability.

Between December 1989 and May 1997, 507 total knee arthroplasties were carried out in 371 patients using the Bi-Surface Knee System (Japan Medical Material, Osaka, Japan) at two institutions and routine rehabilitation program continued for one to two months after TKA. One patient who underwent simultaneous bilateral TKA was excluded because of pulmonary embolism within one month. The other 505 knees (370 patients) were divided into two groups according to the range of flexion after our routine rehabilitation program; one group (Group A: 207 knees) consisted of more than 135 degrees flexion knees and the other group (Group B: 298 knees) consists of less than 135 degrees flexion knees. Patients whose follow-up period was less than 10 years were excluded from this clinical evaluation. Range of flexion was measured preoperatively, at the time after routine rehabilitation program, and at the latest follow-up. Knee function was evaluated on the basis of Knee Society knee score and functional score preoperatively and at the latest follow-up. Kaplan-Meier survivorship analysis was performed with revision for any operation as the end point.

In Group A, the mean preoperative range of flexion was 133.0±16.3 degrees, and at the time after routine rehabilitation program, this improved to 139.7±5.1 degrees. This angle maintained to 136.2±14.3 at the latest follow-up. In Group B, the mean preoperative range of flexion was 111.6±20.4 degrees, and at the time after routine rehabilitation program, this improved to 114.5±13.6 degrees. This angle maintained to 118.2±17.8 at the latest follow-up. The Knee Society knee score and functional score was improved from 43.0±16.9 points and 39.0±20.2 points preoperatively to 95.1±5.8 points and 51.8±21.2 points at the latest follow-up, respectively in Group A. The Knee Society knee score and functional score was improved from 37.1±16.7 points and 31.9±18.4 points preoperatively to 92.5±8.7 points and 53.1±26.1 points at the latest follow-up, respectively in Group B. Kaplan-Meier survivorship at 10-year was 95.5% in Group A and 96.2% in Group B with any operation as the end point. The survivorship between Group A and Group B was not statistically significant.

Good range of flexion was maintained and Knee society score was excellent after a long time follow-up for the patients who achieved deep flexion after TKA. Deep flexion was proved not to affect long term durability in this Bi-Surface Knee System.

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