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Biomedical subjects

V M Goldberg

Publications and source records attributed to V M Goldberg.

At least 19 recordsLinked to original sources
PubMed2001

BMP-2 induction and TGF-beta 1 modulation of rat periosteal cell chondrogenesis.

Periosteum contains osteochondral progenitor cells that can differentiate into osteoblasts and chondrocytes during normal bone growth and fracture healing. TGF-beta 1 and BMP-2 have been implicated in the regulation of the chondrogenic differentiation of these cells, but their roles are not fully defined. This study was undertaken to investigate the chondrogenic effects of TGF-beta 1 and BMP-2 on rat periosteum-derived cells during in vitro chondrogenesis in a three-dimensional aggregate culture. RT-PCR analyses for gene expression of cartilage-specific matrix proteins revealed that treatment with BMP-2 alone and combined treatment with TGF-beta 1 and BMP-2 induced time-dependent mRNA expression of aggrecan core protein and type II collagen. At later times in culture, the aggregates treated with BMP-2 exhibited expression of type X collagen and osteocalcin mRNA, which are markers of chondrocyte hypertrophy. Aggregates incubated with both TGF-beta 1 and BMP-2 showed no such expression. Treatment with TGF-beta 1 alone did not lead to the expression of type II or X collagen mRNA, indicating that this factor itself did not independently induce chondrogenesis in rat periosteal cells. These data were consistent with histological and immunohistochemical results. After 14 days in culture, BMP-2-treated aggregates consisted of many hypertrophic chondrocytes within a metachromatic matrix, which was immunoreactive with anti-type II and type X collagen antibodies. In contrast, at 14 days, TGF-beta 1 + BMP-2-treated aggregates did not contain any morphologically identifiable hypertrophic chondrocytes and their abundant extracellular matrix was not immunoreactive to the anti-type X collagen antibody. Expression of BMPR-IA, TGF-beta RI, and TGF-beta RII receptors was detected at all times in each culture condition, indicating that the distinct responses of aggregates to BMP-2, TGF-beta 1 and TGF-beta 1 + BMP-2 were not due to overt differences in receptor expression. Collectively, our results suggest that BMP-2 induces neochondrogenesis of rat periosteum-derived cells, and that TGF-beta 1 modulates the terminal differentiation in BMP-2 induced chondrogenesis.

Activin Receptors, Type I↗
PubMed2000

Involvement of caspase-3 in epigallocatechin-3-gallate-mediated apoptosis of human chondrosarcoma cells.

Green tea polyphenol-(-)epigallocatechin-3-gallate (EGCG)-is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis. In this study we describe a novel observation that EGCG displayed strong inhibitory effects on the proliferation and viability of HTB-94 human chondrosarcoma cells in a dose-dependent manner and induced apoptosis. Investigation of the mechanism of EGCG-induced apoptosis revealed that treatment with EGCG resulted in DNA fragmentation, induction of caspase-3/CPP32 activity, and cleavage of the death substrate poly(ADP-ribose)polymerase (PARP). Pretreatment of cells with a synthetic pan-caspase inhibitor (Z-VAD-FMK) and a caspase-3-specific inhibitor (DEVD-CHO) prevented EGCG-induced PARP cleavage. The induction of apoptosis by EGCG via activation of caspase-3/CPP32-like proteases may provide a mechanistic explanation for its antitumor effects.

Antineoplastic Agents↗
PubMed2000

Effect of age and sampling site on the chondro-osteogenic potential of rabbit marrow-derived mesenchymal progenitor cells.

Four sequential bone-marrow aspirations from the ipsilateral tibia and iliac crest of New Zealand White rabbits, aged 4 months or 1, 2, or 3 years, were assayed in vitro and in vivo for their chondro-osteogenic potential. Nonhematopoietic cells from the samples of bone marrow were isolated and expanded in culture; their colony-forming efficiency was determined, and second-passage marrow-derived cells, referred to as mesenchymal progenitor cells, were loaded into porous calcium-phosphate ceramic cubes as carrier vehicles for an in vivo cartilage and bone-formation assay. The cubes were placed subcutaneously in nude BALB/C mice for 3 and 6 weeks. On histological examination, the cubes were scored for the presence of bone and cartilage in their pores, and average values for age groups and location were compared. At aspiration, the samples from the iliac crest exhibited an overall reduction in cell concentration with increasing age, and at the first harvest time, they showed a decrease in colony-forming efficiency and cube score with increasing age. This study demonstrated that repeated bone-marrow aspirations may be performed and may have an enhancing effect on the osteochondral progenitor cells of older animals.

Age Factors↗
PubMed2000

Hyaluronan-based polymers in the treatment of osteochondral defects.

Articular cartilage in adults has limited ability for self-repair. Some methods devised to augment the natural healing response stimulate some regeneration, but the repair is often incomplete and lacks durability. Hyaluronan-based polymers were tested for their ability to enhance the natural healing response. It is hypothesized that hyaluronan-based polymers recreate an embryonic-like milieu where host progenitor cells can regenerate the damaged articular surface and underlying bone. Osteochondral defects were made on the femoral condyles of 4-month-old rabbits and were left empty or filled with hyaluronan-based polymers. The polymers tested were ACP sponge, made of crosslinked hyaluronan, and HYAFF-11 sponge, made of benzylated hyaluronan. The rabbits were killed 4 and 12 weeks after surgery, and the condyles were processed for histology. All 12-week defects were scored with a 29-point scale, and the scores were compared with a Kruskall-Wallis analysis of variance on ranks. Untreated defects filled with bone tissue up to or beyond the tidemark, and the noncalcified surface layer varied from fibrous to hyaline-like tissue. Four weeks after surgery, defects treated with ACP exhibited bone filling to the level of the tidemark and the surface layer was composed of hyaline-like cartilage well integrated with the adjacent cartilage. At 12 weeks, the specimens had bone beyond the tidemark that was covered with a thin layer of hyaline cartilage. Four weeks after surgery, defects treated with HYAFF-11 contained a rim of chondrogenic cells at the interface of the implant and the host tissue. In general, the 12-week defects exhibited good bone fill and the surface was mainly hyaline cartilage. Treated defects received significantly higher scores than untreated defects (p < 0.05), and ACP-treated defects scored significantly higher than HYAFF-11-treated defects (p < 0.05). The introduction of these hyaluronan-based polymers into defects provides an appropriate scaffolding and favorable microenvironment for the reparative process. Further work is required to fully assess the long-term outcome of defects treated with these polymers.

Animals↗
PubMed2000

Effect of resin type and manufacturing method on wear of polyethylene tibial components.

The purpose of this study was to examine the effect of ultrahigh molecular weight polyethylene resin type and manufacturing method on wear of Miller-Galante I and II tibial knee components. Thirteen Miller-Galante I and 10 Miller-Galante II components were retrieved at revision surgery. The Miller-Galante I tibial components were made by direct compression molding of Hi-fax 1900 resin and the Miller-Galante II tibial components were made by machining from ram extruded rod of GUR 415 resin. Both generations were gamma radiation sterilized in air. The Miller-Galante I retrievals had significantly more wear damage in the form of scratching and embedded metallic debris, whereas the Miller-Galante II retrievals had significantly more wear damage in the form of delamination. For the implants with an implantation time of 5 years or more, the Miller-Galante II polyethylene had a significantly greater maximum density value than did the Miller-Galante I polyethylene. Examination of thin sections of the Miller-Galante II components revealed that delamination occurred through a subsurface region of severely oxidatively degraded polyethylene; no such subsurface degraded region was observed for the Miller-Galante I components. The results of this study suggest that delamination of polyethylene tibial components that have been gamma radiation sterilized (in air) is influenced by resin type or manufacturing method or both.

Adult↗
PubMed2000

Selection of bone grafts for revision total hip arthroplasty.

The selection of bone grafts to reconstruct deficient bone for revision hip replacement requires an understanding of specific bone graft functions and the critical steps of the biologic incorporation of the graft into the host. Bone grafts provide functions of osteogenesis, either graft derived or by osteoinduction, osteoconduction, or both, and mechanical support. Autologous cancellous bone provides excellent osteogenesis and osteoconduction without structural support. Nonvascularized cortical autografts provide mechanical support and are somewhat osteogenic. Allogeneic cancellous bone is osteoconductive and minimally osteoinductive, whereas cortical allografts provide structural support, if not freeze-dried, and are somewhat osteoconductive. Allogeneic demineralization bone matrix is highly osteoinductive. The selection of the appropriate bone graft depends on the classification of the bone deficiency. Cavitary (contained) defects can be reconstructed with cancellous morselized autograft, frozen or freeze-dried allograft, or allogeneic demineralized bone matrix. Segmental defects require bulk corticocancellous and/or cortical autografts or allografts. The ultimate incorporation of the bone graft depends on the interaction of the graft and the host's mechanical and biologic environment, and host-bone graft contact and stability. Optimum bone graft selection will enhance the clinical outcomes in revision total hip arthroplasty.

Acetabulum↗
PubMed1999

Future directions for research and treatment of osteoarthritis.

Future directions in the research and treatment of osteoarthritis (OA) will be based on the emerging picture of pathophysiological events that govern the initiation and progression of OA. The fundamental event resulting in the destruction of articular cartilage in OA arises from an imbalance between anabolic and catabolic pathways. The extracellular matrix (ECM) of cartilage is degraded by matrix metalloproteinases (MMPs) induced by cytokines. Cytokines also blunt chondrocyte compensatory synthesis pathways required to restore the integrity of the degraded ECM. Inhibition of the MMPs, their activators, and cytokines that induce MMP gene up-regulation would appear to be fertile targets for drug development in the treatment of OA. Restoration of damaged articular surfaces via tissue engineering strategies which could employ chondroprogenitor cells in biomatrices appropriate for transplantation to cartilage surfaces appears feasible. A reduction in cytokine-mediated up-regulation of MMP gene expression as well as augmentation of cartilage ECM biosynthesis may also be possible by employing the principles of gene transfer using suitable vectors that establish long-term stable expression of genes which suppress MMPs while at the same time supporting cartilage ECM biosynthesis.

Animals↗
PubMed1999

Chondroprogenitor cells of synovial tissue.

OBJECTIVE: To assess the chondrogenic potential of cells within the synovium. METHODS: Explants of synovium taken from various sites in the joint were embedded in agarose and cultured with transforming growth factor beta1 (TGFbeta1) to assess their chondrogenic potential. Isolated synovial cells were also tested for their chondrogenic potential by culturing them as aggregates in a chemically defined medium with TGFbeta1. Cartilage formation was determined with histologic staining and immunohistochemistry. The osteochondral potential of the isolated cells was also assessed after subcutaneous implantation of the cells, loaded into porous calcium phosphate ceramic cubes, in athymic mice. RESULTS: A total of 48 synovial explants were cultured in agarose with TGFbeta1. The formation of cartilage was observed in the outer region of 21 explants, and type II collagen was localized in that region by immunohistochemistry. A larger percentage of TGFbeta1+ explants from the inner synovium sites formed cartilage compared with those from the outer synovium sites. Chondrogenesis occurred in aggregates incubated with TGFbeta1 as early as day 7, and by day 14, all TGFbeta1+ aggregates demonstrated chondrogenesis. In contrast with the results of the in vitro aggregate assay for chondrogenesis, no formation of cartilage or bone was evident in any section containing synovial cell-loaded ceramic cubes that were harvested at either 3 or 6 weeks after implantation subcutaneously in athymic mice. CONCLUSION: Synovial explants and isolated synovial cells will undergo chondrogenesis when cultured in the presence of TGFbeta1. The data indicate a possible synovial origin for the chondrocytic cells found in rheumatoid pannus. Furthermore, these data are consistent with the clinical findings of synovial chondrogenesis leading to synovial chondromatosis.

Animals↗
PubMed1999

Bone marrow cells produce soluble factors that inhibit osteoclast activity.

Cytokines that stimulate bone resorption are produced by cells found in bone marrow. However, marrow cells produce multiple factors, some of which may be inhibitors of osteoclast differentiation or activity. Thus, it is not possible to predict a priori whether the mixture of factors produced by marrow cells will have a net stimulatory or inhibitory effect on bone resorption. In this study, we showed that the net effect of whole marrow is to inhibit osteoclast activity induced by parathyroid hormone. Fractionation of the marrow revealed that the inhibitory activity was in the marrow fluid. However, conditioned media obtained from marrow cell cultures also inhibited osteoclast activity. Thus, it is likely that the inhibitory factors are produced in vivo by cells residing in the marrow. These inhibitory factors may represent a physiological regulatory process that plays an important role in maintaining the balance between bone resorption and formation. Because we have previously shown that interleukin-6 is one of the cytokines that parathyroid hormone induces in osteoblastic cells to stimulate osteoclast activity, one potential mechanism by which the marrow-derived inhibitory factors might act is by preventing this production of interleukin-6. However, we found that the marrow cell-conditioned media do not inhibit the production or activity of interleukin-6. Thus, the inhibitory factors appear to block osteoclast activity through a mechanism that does not involve interleukin-6. Taken together, these results demonstrate the importance of factors that inhibit bone resorption and emphasize that the presence of cytokines that stimulate bone resorption in conditions such as osteoporosis and orthopaedic implant loosening should be interpreted with caution unless evidence exists demonstrating their functional importance.

Animals↗
PubMed1999

Hyaluronic acid-based polymers as cell carriers for tissue-engineered repair of bone and cartilage.

Culture-expanded bone marrow-derived mesenchymal progenitor cells differentiate into chondrocytes or osteoblasts when implanted subcutaneously in vivo in combination with an appropriate delivery vehicle. This in vivo implantation technique is used to test new materials as putative delivery vehicles in skeletal tissue-engineering models. HYAFF 11 and ACP sponges, two biomaterials based on hyaluronic acid modified by esterification of the carboxyl groups of the glucuronic acid, were tested as osteogenic or chondrogenic delivery vehicles for rabbit mesenchymal progenitor cells and compared with a well characterized porous calcium phosphate ceramic delivery vehicle. The implant materials were examined by scanning electron microscopy for differences in pore structure or cellular interactions, were quantified for their ability to bind and retain mesenchymal progenitor cells, and were examined histologically for their ability to support osteogenesis and chondrogenesis after subcutaneous implantation into nude mice. The ACP sponge bound the same number of cells as fibronectin-coated ceramic, whereas the HYAFF 11 sponge bound 90% more. When coated with fibronectin, ACP and HYAFF 11 bound, respectively, 100 and 130% more cells than the coated ceramics. HYAFF 11 sponge composites retained their integrity after the 3 or 6-week incubation period in the animals and were processed for histomorphometric analysis. As a result of rapid degradation or resorption in vivo, ACP sponges could not be recovered after implantation and could not be analyzed. HYAFF 11 sponges presented more area available for cell attachment and more available volume for newly formed tissue. Following loading with mesenchymal progenitor cells and implantation, the pores of the sponges contained more bone and cartilage than the pores of ceramic cubes at either time point. Thus, relative to ceramic, HYAFF 11 sponges allow incorporation of twice as many cells and produce a 30% increase in the relative amount of bone and cartilage per unit area. Hence, the hyaluronic acid-based delivery vehicles are superior to porous calcium phosphate ceramic with respect to the number of cells loaded per unit volume of implant, and HYAFF 11 sponges are superior to the ceramics with regard to the amount of bone and cartilage formed. Additionally, hyaluronic acid-based vehicles have the advantage of degradation/resorption characteristics that allow complete replacement of the implant with newly formed tissue.

Animals↗
PubMed1999

Measurement and removal of adherent endotoxin from titanium particles and implant surfaces.

Aseptic loosening is thought to be due primarily to osteolysis induced by cytokines and prostaglandins that are produced in response to implant-derived wear particles. Because endotoxin has many of the same effects as have been reported for wear particles, we hypothesized that adherent endotoxin may be responsible for the biological responses induced by wear particles. We demonstrated the presence of significant levels of adherent endotoxin on commonly used preparations of titanium particles as well as on titanium and titanium-alloy implant surfaces. In contrast, supernatants obtained by centrifugation of particle suspensions contained approximately 1% as much endotoxin as did the particles. Therefore, it is erroneous to assume that particles do not contain endotoxin on the basis of data that it cannot be detected in their supernatants or filtrates. These results emphasize the importance of considering the potential role of adherent endotoxin when examining the in vitro effects of wear particles and the in vivo performance of orthopaedic implants. We also developed a protocol that removed more than 99.94% of the adherent endotoxin from the titanium particles without detectably affecting their size or shape. The removal of adherent endotoxin will allow comparison of the biological responses induced by particles with or without adherent endotoxin.

Endotoxins↗
PubMed1999

Injury to the popliteal artery and its anatomic location in total knee arthroplasty.

Injury to the popliteal artery during total knee arthroplasty (TKA) is a devastating complication. Although infrequent, these injuries can result in the need for further surgery, including revascularization or possibly even amputation. Several mechanisms are capable of producing direct trauma to the popliteal artery, including the use of posterior ret ractors. We investigated the proximity of the popliteal artery to the tibial joint surface during TKA to identify crucial steps in the procedure at which the artery was at highest risk for injury. TKA was performed on cadaveric specimens, and serial intraoperative arteriograms were taken throughout the procedure, demonstrating the potential for arterial injury by the instrumentation. Additionally, 50 transverse magnetic resonance imaging scans of unrelated knees were analyzed for the position of the popliteal artery relative to the midline of the tibial plateau as well as at a level 5 to 10 mm below this, at the site of a typical resection during TKA. All of the arteriograms showed the artery to be a lateral structure at the joint line. Additionally a posterior retractor placed the artery at risk when it was placed in a position lateral to the posterior cruciate ligament or when it was injudiciously inserted more than 1 cm into the soft tissues. Hyperextension of the knee, which might occur during preparation of the patella, produced dramatic tenting of the artery over the posterior joint line. These results demonstrate that the popliteal artery is at significant risk during TKA, particularly if posterior retractors are placed in a position lateral to the midline of the joint. Both hyperflexion and especially hyperextension produced severe deformities and kinking of the artery and would particularly jeopardize an artery with atherosclerosis. Our findings suggest that the popliteal artery may be at least risk during TKA if posterior retractors are placed medial to the midline of the tibial plateau and if care is taken to avoid extremes of both flexion and extension.

Adolescent↗
PubMed1999

Meniscus regeneration in a rabbit partial meniscectomy model.

Meniscectomy is known to be associated with osteoarthrosis of the knee. The purpose of this study was to compare the natural and augmented repair of menisci in the knees of New Zealand White rabbits. To create a partial defect in the medial meniscus, we used an experimental model that has been well characterized and extensively used in the study of osteoarthrosis and articular cartilage repair. The defect was left untreated or treated with one of the following: a periosteal autograft, a type I collagen sponge, or the same sponge loaded with autologous, bone marrow-derived, cultured mesenchymal stem cells. The natural repair was always incomplete and degenerative changes within these joints were progressive. The periosteal autograft underwent differentiation into a bone and hyaline cartilage composite that was ineffectual as a meniscus and accelerated the degenerative changes in those joints when compared to natural repair controls. There was evidence of a consistent sequence of events in the transformation of the periosteal grafts to a core of cartilage that underwent endochondral ossification. In the last two groups, the collagen sponge functioned as a scaffold that resulted in more abundant repair tissue. The collagen sponge alone supported a largely fibrous repair process. The cultured mesenchymal stem cells were observed to augment the repair process in some specimens to include fibrocartilage histologically similar to normal meniscus. Degenerative changes were present in both of these groups, which indicates that the biomechanical function of the meniscus was not restored, or an irreversible osteoarthrosis cascade was initiated during the repair period. Based on these preliminary studies, further investigation of cell-based meniscus regeneration appears to be warranted.

Animals↗
PubMed1999

Clinical and radiographic outcomes of total hip arthroplasty with insertion of an anatomically designed femoral component without cement for the treatment of primary osteoarthritis. A study with a minimum of six years of follow-up.

We evaluated the clinical and radiographic outcomes of 100 consecutive primary total hip arthroplasties in which a proximally coated anatomically designed femoral component was fixed without cement for the treatment of primary osteoarthritis. The minimum duration of follow-up was six years (average, 7.1 years). The eighty-eight patients who had the arthroplasties were followed prospectively with a standard clinical evaluation that involved use of the Harris hip score and a radiographic evaluation based on the criteria of the Hip Society. Bone ingrowth was evaluated with the method of Engh et al. The average age of the patients at the time of the operation was 62.6 years (range, thirty-nine to eighty-four years). Fifty-one patients were men and thirty-seven were women. The average preoperative Harris hip score was 48 points, with an average pain score of 15 points and an average function score of 26 points. Nonmechanical complications that necessitated a revision operation included one deep hematogenous infection, one late periprosthetic fracture, and a 0.5-inch (1.27-centimeter) limb-length discrepancy. At the time of the most recent follow-up, the average Harris hip score was 96 points, with an average pain score of 42 points and an average function score of 45 points. The prevalence of pain in the anterior part of the thigh was 5 percent (five hips). One patient had a revision of the femoral component because of aseptic loosening, and one had a revision of the acetabular component because of recurrent dislocations. Radiographic assessment revealed consistent evidence of proximal bone ingrowth. No complete radiolucent line was identified, except around the stem that had loosened. Twenty-seven femoral components were associated with slight pedestal formation. No osteolytic lesion of the femur was identified. Nonprogressive pelvic osteolysis was identified in four hips, but none of the lesions were more than two millimeters in diameter. None of the acetabular components migrated, and no radiolucent line of more than two millimeters in thickness was seen around any acetabular cup. The data from this study, in which the minimum duration of follow-up was six years, indicate that the anatomically designed prosthesis can provide good results, with low prevalences of pain in the thigh and loosening of the component, in younger, active patients.

Adult↗
PubMed1999

The bone-implant interface: a dynamic surface.

This study quantifies and compares bone formation on and around roughened titanium implants with roughened cobalt chromium, polished solid implants, and titanium fibermetal implants. Cylindrical rods were implanted into the medullary canal of the distal femur of rabbits. The bone-implant interface was studied 3, 6, and 12 weeks after surgery using histomorphometric methods. Roughened surface implants demonstrated significantly more bone directly apposed to the surfaces when compared to the polished or fiber/metal implants at 6 and 12 weeks after surgery. New bone formation and remodeling of bone occurred directly on roughened surfaces as late as 12 weeks after implantation, but not on the unroughened implants. These results suggest that roughening of the surfaces of both titanium and cobalt chromium implants can enhance osseointegration and may be useful clinically for the fixation of prosthetic components.

Animals↗
PubMed1998

In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells.

A culture system that facilitates the chondrogenic differentiation of rabbit bone marrow-derived mesenchymal progenitor cells has been developed. Cells obtained in bone marrow aspirates were first isolated by monolayer culture and then transferred into tubes and allowed to form three-dimensional aggregates in a chemically defined medium. The inclusion of 10(-7) M dexamethasone in the medium induced chondrogenic differentiation of cells within the aggregate as evidenced by the appearance of toluidine blue metachromasia and the immunohistochemical detection of type II collagen as early as 7 days after beginning three-dimensional culture. After 21 days, the matrix of the entire aggregate contained type II collagen. By 14 days of culture, there was also evidence for type X collagen present in the matrix and the cells morphologically resembled hypertrophic chondrocytes. However, chondrogenic differentiation was achieved in only approximately 25% of the marrow cell preparations used. In contrast, with the addition of transforming growth factor-beta 1 (TGF-beta 1), chondrogenesis was induced in all marrow cell preparations, with or without the presence of 10(-7) M dexamethasone. The induction of chondrogenesis was accompanied by an increase in the alkaline phosphatase activity of the aggregated cells. The results of RT-PCR experiments indicated that both type IIA and IIB collagen mRNAs were detected by 7 days postaggregation as was mRNA for type X collagen. Conversely, the expression of the type I collagen mRNA was detected in the preaggregate cells but was no longer detectable at 7 days after aggregation. These results provide histological, immunohistochemical, and molecular evidence for the in vitro chondrogenic differentiation of adult mammalian progenitor cells derived from bone marrow.

Alkaline Phosphatase↗