Author
Louis Lippiello
Other affiliations: Icahn School of Medicine at Mount Sinai
Bio: Louis Lippiello is an academic researcher from Harvard University. The author has contributed to research in topics: Cartilage & Chondrocyte. The author has an hindex of 19, co-authored 28 publications receiving 4875 citations. Previous affiliations of Louis Lippiello include Icahn School of Medicine at Mount Sinai.
Topics: Cartilage, Chondrocyte, Osteoarthritis, Chondrosarcoma, Chondroitin
Papers
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TL;DR: For thirty-two areas of cartilage from nine osteo-arthritic and four "normal" femoral heads a histologic-histochemical grade was assigned as an index of severity of the osteo -arthritic process.
Abstract: For thirty-two areas of cartilage from nine osteo-arthritic and four "normal" femoral heads a histologic-histochemical grade was assigned as an index of severity of the osteo-arthritic process. The DNA and hexosamine concentrations were determined as indicators of cell density and polysaccharide con
2,168 citations
TL;DR: Articular cartilage of the proximal end of the femur from patients with osteo-arthritis and "normal" controls with fractures of neck of femur was obtained at the time of surgical replacement of the Femoral head.
Abstract: Articular cartilage of the proximal end of the femur from twenty-four patients with osteo-arthritis and twenty "normal" controls with fractures of neck of the femur was obtained at the time of surgical replacement of the femoral head and studied by histologic, histochemical, biochemical, and metabol
943 citations
TL;DR: Orthotopic grafting of a rabbit delayed-union model with whole marrow and marrow that had been processed with simple centrifugation significantly increased osteogenesis, as measured biomechanically and biochemically.
Abstract: The osteogenic effect of bone marrow was tested in rabbits, using chambers that had been implanted in the peritoneal cavity (ectopic site) and in a delayed-union model (orthotopic site). Osteogenesis was accelerated in both sites after concentration of marrow elements by centrifugation, but not after unit gravity sedimentation. Chambers that were implanted with marrow that had been processed by simple and isopyknic centrifugation demonstrated a more pronounced increase in deposition of calcium compared with whole-marrow implants of equal volume (101 compared with 193 per cent). Orthotopic grafting of a rabbit delayed-union model with whole marrow and marrow that had been processed with simple centrifugation significantly increased osteogenesis, as measured biomechanically and biochemically. Significantly improved healing was evident radiographically at five weeks after grafting with bone marrow that had been concentrated by simple centrifugation.
292 citations
TL;DR: Three experiments were performed in which the distribution and rates of synthesis of amino sugar-containing macromolecules in normal and osteoarthritic cartilage from the human femoral head were assessed by biochemical analysis and studies of the incorporation of 3H-glucosamine and 35SO4.
Abstract: Since 1960, numerous studies have supported the thesis that the synthetic activity of articular chondrocytes is increased in osteoarthritis, but several recent reports have challenged this concept. To clarify this problem fully and also to define further the products of this increased synthesis, three experiments were performed in which the distribution and rates of synthesis of amino sugar-containing macromolecules in normal and osteoarthritic cartilage from the human femoral head were assessed by biochemical analysis and studies of the incorporation of 3H-glucosamine and 35SO4. The biochemical data obtained clearly demonstrated the previously noted significant decrease in hexosamine content in osteoarthritic tissue. This decrease was principally due to a diminution in glucosamine concentration and correlated inversely with the severity of the disease process (as measured by a previously described histological-histochemical grading system). Metabolic studies showed a marked increment in the rates of incorporation of 3H-glucosamine into both the glucosamine and the galactosamine fractions of the cartilage. The increased synthesis correlated directly in a non-linear fashion with the severity of the disease. The ratio of the rate of incorporation of 3H-glucosamine into the glucosamine fraction to the rate of its incorporation into the galactosamine fraction was the same in normal and osteoarthritic samples, suggesting that the decline in glucosamine concentration was not related to a qualitative alteration of synthetic activity.
246 citations
TL;DR: The data suggest that collagen synthesis in these tissues is substantially greater than in nonosteoarthritic tissues and varies directly with the severity of the disease process up to a point and then varies inversely as the lesion becomes more severe.
Abstract: Collagen metabolism in osteoarthritic human articular cartilage was compared to that in normal cartilage and was also correlated with the degree of severity of the osteoarthritic lesion as determined by a histological-histochemical grading system. No correlation was apparent between the concentrations of DNA, hydroxyproline, and hydroxylysine and the degree of severity of the osteoarthritic lesion (except in far-advanced lesions). Similarly, there was no correlation in levels of these components in tissues from the normal vs. osteoarthritic group. The similarity of the values of the ratio hydroxylysine/hydroxyproline in osteoarthritic tissue compared with normal, and the lack of variation in these with increasing severity of the disease process argues against the possibility that osteoarthritis is associated with a major shift in the synthesis of type II collagen to type I. [3H]Proline incorporation into osteoarthritic cartilage was increased fourfold as compared to normal cartilage and varied with advancing histological-histochemical grade. Measurement of the specific activity of insolubilized hydroxyproline-containing material of the cartilage matrix, as an index of the turnover of collagen, showed a sixfold increase in osteoarthritic cartilage which also varied with grade. These data suggest that collagen synthesis in these tissues is substantially greater than in nonosteoarthritic tissues and varies directly with the severity of the disease process up to a point and then varies inversely as the lesion becomes more severe.
238 citations
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TL;DR: The study of mesenchymal stem cells, whether isolated from embryos or adults, provides the basis for the emergence of a new therapeutic technology of self‐cell repair.
4,861 citations
TL;DR: The OARSI cartilage OA histopathology grading system appears consistent and simple to apply as discussed by the authors, however, further studies are required to confirm the system's utility, as well as their reproducibility and validity.
1,813 citations
TL;DR: A semi-quantitative scoring system that can be applied universally to instability, enzymatic, transgenic and spontaneous OA models may be a useful tool for both new and experienced scorers to sensitively evaluate models and OA mechanisms, and also provide a common paradigm for comparative evaluation across the many groups performing these analyses.
1,701 citations
TL;DR: Graft materials are likely to become more specialized for use in specific clinical applications, and composite preparations may soon provide bone graft materials with efficacy that equals or exceeds that of autogenous grafts.
Abstract: Autograft, allograft, and synthetic bone graft substitute materials play an important role in reconstructive orthopaedic surgery, and understanding the biologic effects of these materials is necessary for optimum use. Although vascularized and cancellous autograft show optimum skeletal incorporation, host morbidity limits autograft availability. Experimental studies have confirmed an immune response to allograft bone, but the clinical significance of this response in humans still is unclear. Small amounts of cancellous allograft in humans usually are remodeled completely; large allografts become incorporated by limited, surface intramembranous bone formation suggesting that these graft are primarily osteoconductive. Several synthetic skeletal substitute materials also are osteoconductive, and may show remodeling characteristics similar to allograft. Demineralized bone matrix and some isolated or synthetic proteins can induce endochondral bone formation, and therefore are osteoinductive. The extent and distribution of remodeling of bone graft materials are influenced by many factors, including the quality of the host site and the local mechanical environment (strain). Graft materials are likely to become more specialized for use in specific clinical applications, and composite preparations may soon provide bone graft materials with efficacy that equals or exceeds that of autogenous grafts.
1,153 citations
TL;DR: The data suggest that collagenase(s) produced by chondrocytes is (are) involved in the cleavage and denaturation of type II collagen in articular cartilage, that this is increased in OA, and that MMP-13 may play a significant role in this process.
Abstract: We demonstrate the direct involvement of increased collagenase activity in the cleavage of type II collagen in osteoarthritic human femoral condylar cartilage by developing and using antibodies reactive to carboxy-terminal (COL2-3/4C(short)) and amino-terminal (COL2-1/4N1) neoepitopes generated by cleavage of native human type II collagen by collagenase matrix metalloproteinase (MMP)-1 (collagenase-1), MMP-8 (collagenase-2), and MMP-13 (collagenase-3). A secondary cleavage followed the initial cleavage produced by these recombinant collagenases. This generated neoepitope COL2-1/4N2. There was significantly more COL2-3/4C(short) neoepitope in osteoarthritis (OA) compared to adult nonarthritic cartilages as determined by immunoassay of cartilage extracts. A synthetic preferential inhibitor of MMP-13 significantly reduced the unstimulated release in culture of neoepitope COL2-3/4C(short) from human osteoarthritic cartilage explants. These data suggest that collagenase(s) produced by chondrocytes is (are) involved in the cleavage and denaturation of type II collagen in articular cartilage, that this is increased in OA, and that MMP-13 may play a significant role in this process.
997 citations