The immunolocalization of the metalloproteinases and their inhibitor, TIMP, in cells and tissues

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Animal Models for Cartilage Regeneration and Repair

Articular cartilage injury and degeneration are leading causes of disability. Animal studies are critically important to developing effective treatments for cartilage injuries. This review focuses on the use of animal models for the study of the repair and regeneration of focal cartilage defects. Animals commonly used in cartilage repair studies include murine, lapine, canine, caprine, porcine, and equine models. There are advantages and disadvantages to each model. Small animal rodent and lapine models are cost effective, easy to house, and useful for pilot and proof-of-concept studies. The availability of transgenic and knockout mice provide opportunities for mechanistic in vivo study. Athymic mice and rats are additionally useful for evaluating the cartilage repair potential of human cells and tissues. Their small joint size, thin cartilage, and greater potential for intrinsic healing than humans, however, limit the translational value of small animal models. Large animal models with thicker articular cartilage permit study of both partial thickness and full thickness chondral repair, as well as osteochondral repair. Joint size and cartilage thickness for canine, caprine, and mini-pig models remain significantly smaller than that of humans. The repair and regeneration of chondral and osteochondral defects of size and volume comparable to that of clinically significant human lesions can be reliably studied primarily in equine models. While larger animals may more closely approximate the human clinical situation, they carry greater logistical, financial, and ethical considerations. A multifactorial analysis of each animal model should be carried out when planning in vivo studies. Ultimately, the scientific goals of the study will be critical in determining the appropriate animal model

Variation in the matrix metalloproteinase-3, -7, -12 and -13 genes is associated with functional status in rheumatoid arthritis

As matrix metalloproteinases (MMPs) play an important role in rheumatoid arthritis, we investigated whether variation in MMP genes was associated with functional disability in rheumatoid arthritis patients. A cohort of patients with seropositive rheumatoid arthritis were recruited and genotyped for the MMP1-1607 1G > 2G, MMP3-1612 5A > 6A, MMP7-153C > T, MMP7-181G > A, MMP12-82A > G and MMP13-77A > G polymorphisms. Genotypes were then analysed in relation to functional disability assessed by Steinbrocker index and Health Assessment Questionnaire (HAQ) score. We detected an association between the MMP13-77 A > G polymorphism and Steinbrocker index, with patients of the A/A genotype having higher score than patients of the A/G or G/G genotype (P = 0.005), and the association remained significant after adjusting for age, sex, erythrocyte sedimentation rate, presence of erosive disease, Ritchie score, prednisolone therapy and years of diagnosis (P = 0.003). We also observed a relationship of Steinbrocker index with the MMP3-1612 5A > 6A, MMP7-181 A > G and MMP12-82A > G polymorphisms (P = 0.082, P = 0.037 and P = 0.045). No association was detected between the MMP1-1607 1G > 2G and MMP7-153C > T polymorphisms and either Steinbrocker index or HAQ score. These results suggest that MMP3, MMP7, MMP12 and MMP13 genotypes may play a role in determining functional status of rheumatoid arthritis

The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model

Conventional clinical therapies are unable to resolve osteochondral defects adequately, hence tissue engineering solutions are sought to address the challenge. A biphasic implant which was seeded with Mesenchymal Stem Cells (MSC) and coupled with an electrospun membrane was evaluated as an alternative. This dual phase construct comprised of a Polycaprolactone (PCL) cartilage scaffold and a Polycaprolactone - Tri Calcium Phosphate (PCL - TCP) osseous matrix. Autologous MSC was seeded into the entire implant via fibrin and the construct was inserted into critically sized osteochondral defects located at the medial condyle and patellar groove of pigs. The defect was resurfaced with a PCL - collagen electrospun mesh that served as a substitute for periosteal flap in preventing cell leakage. Controls either without implanted MSC or resurfacing membrane were included. After 6 months, cartilaginous repair was observed with a low occurrence of fibrocartilage at the medial condyle. Osteochondral repair was promoted and host cartilage degeneration was arrested as shown by the superior Glycosaminoglycan (GAG) maintenance. This positive morphological outcome was supported by a higher relative Young's modulus which indicated functional cartilage restoration. Bone in growth and remodeling occurred in all groups with a higher degree of mineralization in the experimental group. Tissue repair was compromised in the absence of the implanted cells or the resurfacing membrane. Moreover healing was inferior at the patellar groove as compared to the medial condyle and this was attributed to the native biomechanical features