The purpose of this study was to investigate the possible relationship between matrix metalloproteinase-3 (MMP-3) promoter 5A/6A polymorphism and intervertebral disc (IVD) degeneration in the older generation.

One of the important steps in IVD degeneration is disc matrix degradation by matrix degrading enzymes such as MMPs. MMP-3 is one of the potent proteoglycan degrading enzymes and has been suggested to play an important role in IVD degradation. A common 5A/6A polymorphism in the promoter region of the human MMP-3 gene has been identified. This polymorphism was reported to be involved in the regulation of MMP-3 gene expression (the 5A allele has 2-fold higher promoter activity than 6A). We now hypothesize that IVD degeneration is associated with MMP-3 promoter 5A/6A polymorphism.

Forty-nine elderly Japanese volunteers (mean age 74.3 years, range 64–94 years) were studied. Each lumbar disc was graded according to the radiographic classification system of IVD degeneration described by Kellgren and Lawrence. The 5A/6A polymorphism was determined with both single strand conformation polymorphism (SSCP) and polymerase chain reaction with allele-specific primers (AS-PCR).

Two subjects (4%) with 5A5A genotype, 16 (33%) with 5A6A, and 31 (63%) with 6A6A were observed. Genotype was totally independent of age and sex. There was a significantly larger number of IVDs graded 2 and higher in the 5A/5A+5A/6A than in the 6A/6A (p< 0.05). The degenerative scores of lumber discs were also distributed more highly in the 5A/5A+5A/6A than in the 6A/6A (p=0.0029).

Many environmental factors have been reported to accelerate IVD degeneration. Recently, genetic factors have also been highlighted as possible risk factors. The 5A allele of the human MMP-3 promoter is a possible risk factor for acceleration of IVD degeneration in people aged over 64 years old. We conclude that MMP-3 plays a key role in the degeneration of IVD in the older generation.

Introduction: The importance of soft tissue balance in total knee arthroplasty (TKA) has been documented, and several authors have documented operative procedure of soft tissue release for soft tissue balancing. However, the quantity of change of soft tissue balance in each procedure has not been reported in detail, and the importance of each procedure of soft tissue release has not been well argued. This study is a quantitative evaluation of the effect of soft tissue release on soft tissue balance in TKA.

Materials and methods: Forty-five varus knees in 42 patients with a preoperative femorotibial angle (FTA) of more than 180°underwent TKAs from 1996 to 2000, and these knees were evaluated in this study. The mean age of the subject was 70.1 years (from 33 to 87 years), including 5 knees in male and 40 knees in female. The extension and flexion gap of the knee joint was measured by the instrument applying the force of the moment of 50kg& #65381;cm to each medial and lateral joints. We decided the procedure of soft tissue balancing as follows and the extension and flexion gap were measured in each steps. The procedure were 1) exposure of posterior medial aspects of the tibia with release of the attachment of semimembranosis, 2) removal of osteophytes from the medial distal femur and proximal tibia, 3) resection of the posterior cruciate ligament (if necessary), 4) release of the superficial medial collateral ligament (MCL), 5) resection of the superficial MCL (if necessary).

Results: The results of the change of the extension and flexion gap in each procedure were shown as below. Final gap was calculated as the difference against medial extension gaps.

Procedure: The change of extension gap The change of flexion gap medial lateral medial lateral 1) (n=45) 1.2 ± 1.4 1.2 ± 1.2 1.9 ± 2.2 1.7 ± 2.6 2) (n=36) 1.9 ± 2.5 0.7 ± 1.2 1.7 ± 1.6 1.3 ± 2.0 3) (n=19) 1.8 ± 1.5 1.9 ± 1.8 2.7 ± 2.0 2.9 ± 2.2 4) (n=18) 2.0 ± 1.9 0.3 ± 0.5 2.4 ± 1.7 0.9 ± 1.1 5) (n=4) 2.8 ± 2.3 0.4 ± 0.8 4.1 ± 1.5 1.5 ± 1.4 Final gap 0 3.4 ± 2.6 0.5 ± 3.1 3.1 ± 3.4

Discussion: The change of soft tissue balance in each soft tissue procedure in TKA was evaluated quantitatively in this study. The amount of the changes in each steps were few and differed with cases. The procedure for medial osteophytes and MCL had a tendency of efficacy to medial tightness against lateral in knees with varus deformity.

A hydroxyapatite/type I collagen(HAp/Col) composite, in which the hydroxyapatite nanocrystals align along the collagen molecules, has been prepared. The bio-compatibility, osteoconductive activity and efficacy as a carrier of rhBMP-2 of this novel biomaterial were examined. Following three studies were performed – (1) The composite materials (4×4×1mm³) were implanted in the back of Wistar rats, and specimens collected for histological observations until week 24. (2) The composite materials (5×5×10mm³) containing rhBMP-2(0, 200, 400μg/ml) were grafted in radii and ulnae in beagle dogs. X-ray images were prepared, and specimens collected for histological observation at week 8 and 12. (3) The implants(15mm in diameter and 20mm in length) containing rhBMP-2 (0, 400 mg/ml) were implanted in tibiae in beagle dogs and fixed with Ilizarov method. Soft x-ray images were prepared each week. The bone mineral density was measured and the implants were harvested at 12, 18 and 24 weeks after surgery. The period until bone union after implantation of the HAp/Col implant was between 10 and 12 weeks after operation, and approximately the same as that of autogenous bone graft. Histological analysis revealed that osteoclasts appeared in a Howship’s lacunae-like structure formed on the composite and osteoblasts arranged on the newly formed bone. These findings suggest that the HAp/Col composite has a character similar to that of natural bone. X-ray images and histological findings for the composites support the idea that HAp/Col has a high osteoconductive activity and is able to induce bone-remodeling units. In cases where the implants are grafted at weight bearing sites, treatment with rhBMP(400μg/ml) may be useful to shorten the time until bone union.