Limited Repair Research Articles

PPARδ Agonist Promotes Type II Cartilage Formation in a Rabbit Osteochondral Defect Model.

Osteoarthritis (OA) is a chronic degenerative joint disease accompanied by an inflammatory milieu that results in painful joints. The pathogenesis of OA is multifactorial, with genetic predisposition, environmental factors, and traumatic injury resulting in the direct or indirect loss of cartilage. The articular cartilage can also be damaged by direct focal traumatic injury. Articular cartilage provides a smooth, deformable bearing surface with a low coefficient of friction, increased contact area, and reduced contact stress. Articular type II hyaline cartilage lines the synovial joints and, when injured, has a limited ability for repair, except for the most superficial layers via diffusion from the synovial fluid, secondary to no blood supply, a complex structure, and a low metabolic rate. Restoring the articular surface can relieve pain and restore function. Although many strategies have been developed to regenerate type II collagen based on the extent of the lesion, surgical treatments are still evolving. The peroxisome proliferator-activated receptor delta (PPARδ) agonist and collagen treatment of mesenchymal stem cells (MSCs) enhance the chondrogenic capacity in vitro. We present a novel technique for cartilage restoration in a rabbit cartilage osteochondral defect model using a PPARδ agonist (GW0742)-infused 3D collagen scaffold to induce type II cartilage from MSCs.

Limited vs. extended repair for acute type I aortic dissection: long-term outcomes over a decade in Beijing Anzhen Hospital.

Limited vs. extended repair for acute type I aortic dissection: long-term outcomes over a decade in Beijing Anzhen Hospital.

Purified collagen I oriented membrane for tendon repair: An ex vivo morphological study

Injured tendons have limited repair ability after full-thickness lesions. Tendon regeneration properties and adverse reactions were assessed ex vivo in an experimental animal model using a new collagen I membrane. The multilamellar membrane obtained from purified equine Achilles tendon is characterized by oriented collagen I fibers and has been shown to sustain cell growth and orientation in vitro. The central third of the patellar tendon (PT) of 10 New Zealand White rabbits was sectioned and grafted with the collagen membrane; the contralateral PT was cut longitudinally (sham-operated controls). Animals were euthanized 1 or 6 months after surgery, and tendons were subjected to histological and Synchrotron Radiation-based Computed Microtomography (SRµCT) examination and 3D structure analysis. Histological and SRµCT findings showed satisfactory graft integration with native tendon. Histological examination also showed ongoing angiogenesis. Adverse side-effects (inflammation, rejection, calcification) were not observed. The multilamellar collagen I membrane can be considered as an effective tool for tendon defect repair and tendon augmentation.

Neuronal Nitric Oxide Synthase (nNOS)/NO, An Accelerator of Melanoma Progression, is a Potential Target for Chemoprevention

Neuronal Nitric Oxide Synthase (nNOS)/NO, An Accelerator of Melanoma Progression, is a Potential Target for Chemoprevention

Osteochondral Lesions of the Talus

Osteochondral lesions of the talus can present as a late complication of ankle injuries. As the talus is largely covered by articular cartilage, it has a limited ability for repair. Early and accurate diagnosis is important as talar integrity is required for optimal function of the ankle. The common presentation is chronic ankle pain with a history of ankle trauma. Conservative treatment involving a period of casting and non-weight-bearing is recommended for acute, non-displaced osteochondral lesions. Surgical management is recommended for unstable lesions or failed conservative management. Key words: Ankle sprains, Arthroscopy, Cartilage culture, Osteochondral graft

Dementia

The human brain is largely postmitotic, with limited ability for repair or regeneration in response to age- or disease-related neuropathologic alterations. The study by Schneider et al.1 provides a sobering view of our brain’s longevity by showing that the majority of older community-dwelling persons, regardless of the presence or absence of dementia, have significant brain pathology, not just one pathology but several. Schneider et al. examined the brains of 141 volunteers who had undergone careful (longitudinal) clinical screenings for this clinical-pathologic cohort study of aging. They concluded that the majority of these older individuals had neuropathology that could have a functional impact, and that those persons with multiple pathologies were more likely to have overt signs of dementia. As better treatments for non-CNS medical conditions allow our elderly population to live longer, the impact of this age-associated neuropathology should be of concern to neurologists managing geriatric patients. There have been previous studies of aging neuropathology showing significant abnormalities in the brain before dementia develops2–4; …

The diagnosis and management of osteochondral lesions of the talus: osteochondral allograft update

m m m b p b e w f he management of osteochondral defects of the talus remains a clinical challenge as a result of the oor intrinsic healing potential of cartilage. Osteohondral lesions of the talus (OLT) is a relatively ommonly cause of ankle pain and disability (Fig 1). artilage has very limited ability for repair or regenration. A biologic solution to the repair of significant artilage defects is the “holy grail.” Some of the bstacles to cartilage repair are the fact that it is highly ascular, hypocellular, and the chondrocytes are “imrisoned” in a matrix (Fig 2). General surgical strategies have consisted of inducng a repair response through microfracture-forming brocartilage. Autologous chondrocyte implantation ACI) has also been used and has some promising esults. We discuss repairing these lesions with an ntact hyaline cartilage organ structure. Osteochondral allografting is a surgical option for steochondral lesions involving the talar dome in paients who have failed non-operative management. llografts are particularly useful for avascular necrois, for larger lesions with more extensive disease, or s a salvage procedure for failed autografting or subhondral perforation. Unlike other surgical strategies hat attempt to stimulate the generation or regeneraion of fibrocartilage through a repair response, the ransplantation of an osteochondral allograft involves lling the defect with viable chondrocytes and an ntact hyaline cartilage organ structure.1-5 The advantages of using allograft are a decrease in atient morbidity, shorter surgical time, smaller inciions, tissue flexibility, and the ability to resurface

Origin and persistence of the mitochondrial genome.

The mitochondrial genome comprises a circular, histone-free 'chromosome' of 16.6 kb of DNA, present in one or more copies in every mitochondrion. This chromosome has been tightly conserved for more than half a billion years, coding in every multicellular animal so far investigated, both vertebrate and invertebrate: (i) the same 13 protein subunits required for oxidative phosphorylation; (ii) a component of each of the two mitochondrial ribosome subunits; and (iii) the 22 transport RNAs present within the mitochondrion. Exons on the circle are tightly packed, with no spacing introns. Mitochondrial DNA is histone-free, has limited repair ability, and has a relatively high mutation-fixation rate. Inheritance is cytoplasmic and maternal, with epidemiological evidence (namely the familial distribution of polymorphisms) indicating that recombination with mtDNA of paternal origin is exceedingly rare. Thus the maintenance and evolution of mtDNA (its remarkably successful symbiotic persistence with the nuclear genome) has been essentially asexual. The machinery for homologous recombination is present in mitochondria of at least some species, however, and it might be surprising if it did not occur between circles in some circumstances. By bringing together the fields of mitochondrial biochemistry, evolutionary genetics, reproductive physiology, and neuromuscular medicine in focusing on the inheritance of normal and abnormal human mtDNA, we can hope to better understand the forces behind this genome's inheritance and what might be required of ovarian function to satisfy its accurate persistence over millions of years. Clinically we can hope also for a better understanding of ooplasmic factors in human fertility and in the wide manifestations of mitochondrial genomic disease.

Isolation of a cDNA sequence of rabbit GDF5 (mature form) and pattern of its mRNA expression during periosteal chondrogenesis.

Articular cartilage has a limited ability for repair and/or regeneration. Periosteal grafts, having chondrogenic potential, are used clinically and in experimental models to study the repair and regeneration of cartilage. Growth/differentiation factor 5 (GDF5), recently shown to be involved in chondrogenesis and normal skeletal development, is a bioactive candidate for augmenting the repair of damaged cartilage. In order to investigate the role of GDF5 during periosteal chondrogenesis, the rabbit sequence must be known, as most experimental models involve rabbit tissues. For this purpose, the complete rabbit-specific cDNA sequence of the mature form of GDF5 was determined. Mature rabbit GDF5 was found to be 100% identical to that of human GDF5 at the amino acid level. Using the cDNA sequence, specific primers for PCR were designed. Quantitative RT-PCR, using rabbit-specific primers, showed up-regulation of GDF5 mRNAs early during periosteal chondrogenesis suggesting its potential involvement in this process. The timing and magnitude of this expression was markedly stimulated by TGF-beta 1, which has already been shown to be a potent inducer of periosteal chondrogenesis.

Oxidative enzyme metabolism in rabbit intrasynovial flexor tendons. I. Changes in enzyme activity of the tenocytes with age

Clinically, the results of surgical repair to tendons within the digital canal are generally unsatisfactory. It is not known whether the tendon cells themselves have the capacity to effect repair, or whether dependence on surrounding tissues is necessary. Our lack of understanding of these problems is partly due to an inadequate knowledge of tendon metabolism. The activities of three oxidative enzymes, succinate dehydrogenase (citric acid cycle), glucose-6-phosphate dehydrogenase (pentose phosphate pathway), and lactate dehydrogenase (glycolysis), were measured in flexor tendons of young and adult rabbits. The same enzymes were also measured in rat liver for comparison. The results showed that adult tenocytes were entirely dependent on anaerobic metabolism for their energy supply, and that their biosynthetic capability for nucleic acid and fat production was extremely limited. In contrast, the synovium was more active metabolically, and might be expected to have a greater capability for repair following injury. Young rabbit tenocytes were somewhat more active metabolically, and showed some capacity for aerobic metabolism and production of cofactors for biosynthesis. Generally, however, rabbit tendon as a whole would appear to have only a limited ability for repair, based on its metabolic activity. There are areas of fibrous cartilage within the tendon which always occur at regions subject to particular stress. These regions were metabolically more active than the tendon itself.