Introduction Current cell therapy for cartilage regeneration requires invasive procedures, periosteal coverage and scaffold use. We have developed a novel transplantation method with synovial mesenchymal stem cells (MSCs) to adhere to the cartilage defect.

Import of proteins across the inner mitochondrial membrane through the Tim23:Tim17 translocase requires the function of an essential import motor having mitochondrial 70-kDa heat-shock protein (mtHsp70) at its core. The heterodimer composed of Pam18, the J-protein partner of mtHsp70, and the related protein Pam16 is a critical component of this motor. We report that three interactions contribute to association of the heterodimer with the translocon: the N terminus of Pam16 with the matrix side of the translocon, the inner membrane space domain of Pam18 (Pam18 IMS ) with Tim17, and the direct interaction of the J-domain of Pam18 with the J-like domain of Pam16. Pam16 plays a major role in translocon association, as alterations affecting the stability of the Pam18:Pam16 heterodimer dramatically affect association of Pam18, but not Pam16, with the translocon. Suppressors of the growth defects caused by alterations in the N terminus of Pam16 were isolated and found to be due to mutations in a short segment of TIM44, the gene encoding the peripheral membrane protein that tethers mtHsp70 to the translocon. These data suggest a model in which Tim44 serves as a scaffold for precise positioning of mtHsp70 and its cochaperone Pam18 at the translocon.

Strenuous running of rats enhances mechanical stress on the knee, thereby inducing degeneration of articular cartilage. Bone morphogenetic protein-7 (BMP-7) has an inhibitory effect on cartilage degeneration, suggesting its usefulness for human osteoarthritis patients. However, its mode of administration should be investigated. We examined whether weekly knee injections of BMP-7 delayed the progression of cartilage degeneration. Wistar rats were forced to run 30 km in 6 weeks on a rodent treadmill, and BMP-7 was injected weekly into the knee. Macroscopically and histologically, this strenuous running regimen induced cartilage degeneration. Weekly injections of 250 ng BMP-7 delayed the progression of cartilage degeneration. Immunohistochemically, in the control knee, type II collagen expression decreased, while BMP-7 expression in chondrocytes slightly increased. Interestingly, weekly injection of BMP-7 increased BMP-7 expression even 9 days after the final injection. Disulfate disaccharide keratan sulfate in serum transiently increased in the control group, while it remained at a low level in the BMP-7 group. Weekly BMP-7 injection increased BMP-7 expression in chondrocytes and its effect seemed to last more than 7 days. The effect of BMP-7 could be monitored by serum keratan sulfate concentration. Periodical injections of BMP-7 delayed progression of cartilage degeneration induced by excessive running in rats. Keywords: BMP-7; articular cartilage; strenuous running; keratan sulfate; weekly injection Osteoarthritis (OA) in the knees constitutes an increasingly common medical problem for aging people. 1 Mechanical stress is one of the factors contributing to the progression of OA. Strenuous running of rats enhances mechanical stress on weight bearing joints, inducing OA of the knees. 2,3 This model requires no surgery or drugs, making it possible to detect subtle changes accompanying OA.Bone morphogenetic proteins (BMPs) have a variety of biological effects including enhancement of cartilage repair. 4 Among BMPs, BMP-7 is especially attractive, because it is one of two BMPs already approved for clinical use in various applications by the FDA. Recent data from an anterior cruciate ligament transection model in rabbits demonstrated that continuous intraarticular infusion of BMP-7 had a protective effect on cartilage degeneration, 5 suggesting the possible utility of BMP-7 as a treatment for human OA patients. However, given the challenges associated with clinical delivery by continuous infusion, further consideration should be given to the mode of administration.We speculated that periodic injections of BMP-7 into the knee joint might suppress the loss of cartilage matrix and consequently prevent OA progression. The purpose of this study was to examine whether weekly knee injections of BMP-7 delay development of OA and to investigate the possible mechanisms for this action in a strenuous running model of OA in rats. MATERIALS AND METHODS Strenuous Running of RatsWistar rats at 15-16 weeks of age (Sankyo L...

Introduction We investigated the ability of a weekly intraarticular injection of bone morphogenetic protein (BMP)-7 to prevent osteoarthritis in rabbits with anterior cruciate ligament transections.

Background: Mitochondrial import motor associates with inner membrane translocase TIM23 by undefined interactions. Results: Site-specific photo-cross-linking was detected between matrix loops of TIM23 subunits Tim23 and Tim17 with Tim44 and Pam17, respectively. Conclusion: Motor components are tethered to translocon via the scaffold Tim44, with regulatory protein Pam17 having independent interaction site. Significance: Defined motor translocon architecture provides foundation for mechanistic understanding of efficient regulated translocation.