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Biomedical subjects

E Livne

Publications and source records attributed to E Livne.

At least 19 recordsLinked to original sources
PubMed2007

Systemic treatments with the low-calcemic 1,25(OH)(2)D(3) analogs JKF or QW increase both the morphological and biochemical responses to estradiol-17beta in rat tibiae.

We demonstrated previously that daily injection for 3 days of the less calcemic vitamin D analogs: JK 1624 F(2)-2 (JKF) and QW 1624F(2)-2 (QW) followed by estradiol-17beta (E(2)) in female rats upregulated creatine kinase-specific activity (CK) in skeletal tissues. In this study, we evaluated both histomorphological and biochemical changes due to a regime of 4 days treatment with JKF or QW, followed by injection of E(2) on day 5, repeated for 2.5 months. Ovariectomized female rats (Ovx) were injected 2 weeks after surgery, with JKF or QW at 0.2 ng/g BW followed by injections of E(2) (1 microg/rat) on day 5 of each week for 2.5 months. Rats were sacrificed 24 h after the last injection and bones were analyzed. JKF alone decreased growth plate width, increased % total bone volume (%TBV), with no change in cortical thickness. In contrast, QW restored growth plate width and %TBV with no change in cortical thickness. Combined with E(2), JKF restored %TBV and growth plate width but with no change in cortical thickness, while QW restored significantly all parameters including cortical thickness. Moreover, there was also an increase in the responsiveness of CK to E(2) in epiphyseal cartilage and diaphyseal bone but not in uterus. Thus, vitamin D less calcemic analogs increased responsiveness to E(2) morphologically as well as biochemically. We, therefore, conclude that combined treatment of less calcemic analogs vitamin D and E(2) might be superior for treatment of bone damage caused by ovariectomy in female rats and might be applied for post-menopausal osteoporosis.

Animals↗
PubMed2005

Microscopy analysis of bone marrow-derived osteoprogenitor cells cultured on hydrogel 3-D scaffold.

Bone marrow contains progenitor cells that are able to differentiate into several mesenchymal lineages, including bone. These cells may also provide a potential therapy for bone repair. The purpose of this study was to select the osteoprogenitor cell subpopulation from bone marrow-derived mesenchymal stem cells (MSCs) and to test the ability of a hydrogel scaffold to support growth and osteogenic differentiation. MSCs isolated from rat femur bone marrow were cultured in DMEM medium supplemented with antibiotics, FCS, and L-glutamine. Osteogenic supplements (dexamethasone, sodium beta-glycerophosphate, and ascorbic acid) were added for one, two or three weeks. A selective subpopulation of osteoprogenitor cells was identified by immunohistochemistry, general morphology, scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). Committed osteogenic cells were transferred to a 3-D hydrogel scaffold and cultured for an additional week. In standard culture, the osteoprogenitor cells formed cell clusters identified by Alizarin red S staining and by positive osteocalcin immunostaining. The number of osteoprogenitor cells, matrix synthesis, and mineralization increased gradually up to three weeks in culture. Mineral deposition in the matrix analyzed by EDS revealed the presence of calcium and phosphate ions at a Ca/P molar ratio of 1.73 in both the osteogenic cultures and the scaffold osteoprogenitor culture. Histological preparations revealed cell clusters within the hydrogel scaffold and SEM analysis revealed cell clusters attached to the scaffold surface. It is concluded that the hydrogel scaffold can support growth and differentiation of osteogenic cultures including mineralization and can potentially serve as a bone graft substitute containing committed osteoprogenitor cells.

Animals↗
PubMed2005

Bone marrow stem cells and biological scaffold for bone repair in aging and disease.

The loss of bone mass observed in aging enhances the risk of fractures. The process of bone repair in aging is slow and limited due to reduced activity of the osteoblasts. Bone marrow stem cells (MSCs) residing in the bone marrow are the progenitors for osteoblasts. The ability to enhance healing of bone defect in aging by MSCs can contribute in the prevention of the complications resulting from long-term immobilization that are especially fatal in old age. Our aim was to test the ability of MSCs inserted into a biological scaffold to enhance bone defect repair. Osteoprogenitor cells were selected from rat bone marrow stem cells cultured in DMEM medium supplemented with FCS, antibiotics, ascorbic acid, beta-glycerophosphate, and dexamethasone. The selected osteogenic subpopulation was identified by osteocalcin immunohistochemistry as well as Alizarin red S and von Kossa staining which are specific for bone matrix and mineral deposition. Committed osteoprogenitor cells cultured on the hydrogel scaffold were transplanted into the area of a rat tibia segmental bone defect and examined after 6 weeks. Radiology images revealed that 6 weeks post-implantaion, calcified material was present in the site of the defect, indicating new bone formation. It is concluded that committed osteogenic MSCs contained in a biocompatible scaffold can provide a promising surgical tool for enhancement of bone defect healing that will minimize the complications of bone repair in aging and disease.

Aging↗
PubMed2005

Serum vascular endothelial growth factor as a significant marker of treatment response in pediatric malignancies.

The aim of this pilot study was to determine VEGF serum levels (S-VEGF) at diagnosis and at restaging in children diagnosed with cancer, and to investigate whether this parameter provides prognostic information for remission after induction therapy and response to treatment. S-VEGF levels of 35 consecutive pediatric patients with various types of cancer were assayed at diagnosis and at restaging. Levels of VEGF were determined using a commercially available ELISA anti-human VEGF immunoassay kit. Thirty-one children went into complete remission or had a very good partial response to first-line therapy; 4 patients developed tumor progression. At diagnosis average S-VEGF level was 495 pg/mL (range, 0.89--2220 pg/mL) and at restaging it decreased to 118.36 pg/mL (range, 7.44--487 pg/mL). (p=.0039). The 4 patients with tumor progression had increased S-VEGF levels at restaging. The comparison between the levels of S-VEGF at diagnosis and at restaging showed a significant difference for the patients who responded to treatment with decreased S-VEGF and the patients who developed tumor progression with increased S-VEGF (p=.0019). One child with metastatic Ewing sarcoma developed progressive disease after several weeks, with significantly progressively higher S-VEGF levels. One child with Hodgkin disease, who had a higher level at first restaging and developed progressive disease, responded to reinduction therapy and had a significantly lower level at the second restaging. The child with metastatic hepatoblastoma responded to first-line chemotherapy with concomitant decrease in S-VEGF and alpha-fetoprotein levels, but developed local recurrence with elevation in both parameters. Changes in S-VEGF levels correlated with response to treatment for most of the children diagnosed with cancer. This provides a rationale for exploring clinical interest in S-VEGF measurements of a larger group of children with malignancies, and using the test for clinical trials of antiangiogenic therapies.

Adolescent↗
PubMed2004

Bone defect repair in rat tibia by TGF-beta1 and IGF-1 released from hydrogel scaffold.

Bone repair is one of the major challenges facing reconstructive surgery. Bone regeneration is needed for the repair of large defects and fractures. The ability of TGF-beta1 and IGF-1 incorporated into hydrogel scaffold to induce bone regeneration was evaluated in a rat tibia segmental defect model. External fixation was performed prior to the induction of the segmental bone defect in order to stabilize the defect site. Hydrogel scaffold containing either TGF-beta, IGF-1, TGF-beta + IGF-1, hydrogel containing saline or saline, were inserted in the defect. Calcified material was observed in the defects treated with TGF-beta 2 weeks following the start of treatment. Bone defects treated with TGF-beta, IGF-1 or TGF-beta + IGF-1 revealed significant bone formation after 4 and 6 weeks when compared to the control specimens. X-ray images showed that solid bone was present at the defect site after 6 weeks of treatment with TGF-beta or TGF-beta + IGF-1. A less pronounced bone induction was observed in the control specimens and bones treated with IGF-1. Percent closure ratio of bone defects after 6 weeks were 40, 80, 89, and 97% for saline, hydrogel, IGF-1, TGF-beta and IGF-1 + TGF-beta groups, respectively. It is concluded that hydrogel scaffold can serve as a good osteoconductive matrix for growth factors, and that it provides a site for bone regeneration and enhances bone defect healing and could be used as alternative graft material.

Animals↗
PubMed2004

Site specific changes in gene expression and cartilage metabolism during early experimental osteoarthritis.

OBJECTIVES: To characterize the molecular events underlying cartilage injury in the early phase of mono-iodoacetate-induced osteoarthritis (OA) in rats. METHODS: Experimental osteoarthritis was induced by intra-articular injection of 0.03mg mono-iodoacetate (MIA) in Wistar rats. Animals were killed 2, 5, 10, 15 and 20 days post-injection. Synovial tissue and standardized biopsies from different areas of knee cartilage were examined. Proteoglycan synthesis ((35)S incorporation) and gelatinase activities (zymography), semi-quantitative RT-PCR and immunohistochemistry for IL1beta, iNOS, COX2 and PPARgamma, were performed on these samples. RESULTS: Changes in proteoglycan synthesis and gelatinase activities were time and site-dependent. Proteoglycan synthesis inhibition was maximal by day 2 while the highest gelatinase activities were observed at day 5. Central part of patella and posterior plateaus and condyles, i.e. the weight-bearing cartilage areas, were the most affected. IL1beta and iNOS transcripts were induced early in cartilage at time of maximal proteoglycan synthesis inhibition, especially in weight-bearing areas. COX-2 was slightly up-regulated whereas PPARgamma gene expression remained unchanged. Gene expression profile in synovium paralleled that of cartilage, except for PPARgamma which was up-regulated at day 15 and 20. Immunostaining for IL1beta and iNOS showed that proteins were located in diseased cartilage areas at early stage of the experimental OA (day 2). At later time-points (day 20), IL1beta and iNOS were expressed in perilesional areas whereas immunostaining became below control level for COX-2 and PPARgamma. CONCLUSIONS: Time-dependent degradation of cartilage after injection of low dose of MIA (0.03mg) into rat knee joint can be related to early loss of proteoglycan anabolism, increased gelatinase activities and expression of IL1beta and downstream inflammatory genes. Increased susceptibility to MIA in weight-bearing areas of cartilage further indicate that MIA-induced experimental OA is a relevant model to study not only metabolical but also biomechanical aspects of human OA.

Animals↗
PubMed2002

Enhancement of bone defect healing in old rats by TGF-beta and IGF-1.

Bone defects are often created in order to repair bone pathologies. In the aging population, the healing of such defects is very limited. Bone healing in aging depends on the availability of various hormone and growth factors. The ability of growth factors to enhance bone formation in femoral defects in old rats was tested. Bone defects were induced in femurs of old rats. A single dose of transforming growth factor-beta (TGF-beta), IGF-1, TGF-beta+IGF-1 or saline was inserted in the defect and bones were tested after 2 and 4 weeks. Radiology revealed that mineralization appeared in the 2 weeks group in defects treated with TGF-beta and in defects treated with TGF-beta, TGF-beta+IGF-1 in the 4 weeks groups. Computerized tomography (CT) coronal and axial images revealed that 4 weeks after treatment with TGF-beta+IGF-1, a complete bone bridge was observed. Morphology revealed that these defects were filled with trabecular bone. A less pronounced bone healing was observed after TGF-beta or IGF-1, while control specimens revealed partial healing of the bone defect. Biomechanical tests indicated that treatment with TGF-beta, IGF-1 or TGF-beta+IGF-1 resulted in a significant increase of bone bending rigidity compared to control in the 4 weeks group and that TGF-beta+IGF-1 was the most inductive in this respect. The ability to induce bone healing in aging by TGF-beta+IGF-1 is of a great clinical importance for restoration of bone strength and biomechanical properties of bone defects in aging.

Aging↗
PubMed2001

Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes.

The study of human cardiac tissue development is hampered by the lack of a suitable in vitro model. We describe the phenotypic properties of cardiomyocytes derived from human embryonic stem (ES) cells. Human ES cells were cultivated in suspension and plated to form aggregates termed embryoid bodies (EBs). Spontaneously contracting areas appeared in 8.1% of the EBs. Cells from the spontaneously contracting areas within EBs were stained positively with anti-cardiac myosin heavy chain, anti--alpha-actinin, anti-desmin, anti--cardiac troponin I (anti-cTnI), and anti-ANP antibodies. Electron microscopy revealed varying degrees of myofibrillar organization, consistent with early-stage cardiomyocytes. RT-PCR studies demonstrated the expression of several cardiac-specific genes and transcription factors. Extracellular electrograms were characterized by a sharp component lasting 30 +/- 25 milliseconds, followed by a slow component of 347 +/- 120 milliseconds. Intracellular Ca(2+) transients displayed a sharp rise lasting 130 +/- 27 milliseconds and a relaxation component lasting 200--300 milliseconds. Positive and negative chronotropic effects were induced by application of isoproterenol and carbamylcholine, respectively. In conclusion, the human ES cell--derived cardiomyocytes displayed structural and functional properties of early-stage cardiomyocytes. Establishment of this unique differentiation system may have significant impact on the study of early human cardiac differentiation, functional genomics, pharmacological testing, cell therapy, and tissue engineering.

Actinin↗
PubMed2000

Differential metabolic responses to local administration of TGF-beta and IGF-1 in temporomandibular joint cartilage of aged mice.

Osteoarthritis is a degenerative joint disease characterized by destruction of the articular cartilage in aging and senescence. The aim of this study was to study the possible treatment of this disease by intraarticular injection of growth factors to osteoarthritic joints of aged animals. 20-month-old female ICR mice were injected with insulin-like growth factor (IGF-1), transforming growth factor-beta (TGF-beta) or TGF-beta+IGF-1 on days 1, 4, and 7. On day 9 the joints were dissected and cultured in the presence of 35S-sulfate and 3H-thymidine. Combined treatment of TGF-beta and IGF-1 resulted in elevated 3H-thymidine incorporation and DNA and protein contents, reduction of 35S-sulfate incorporation and alkaline phosphatase activity, with no significant change in the activity of acid phosphatase. Following injections of TGF-beta, contents of DNA and protein, and incorporations of 3H-thymidine were induced, and 35S-sulfate and alkaline phosphatase activity were reduced. Treatment with IGF-1 resulted in reduced incorporation of 3H-thymidine with no significant changes in the activity of acid phosphatase. Atypically hypertrophic chondrocytes were observed along the articular surface and the endogenous production of TGF-beta and of IGF-1, as revealed by immunohistochemistry, was reduced. It is concluded that although 3H-thymidine incorporation and alkaline phosphatase activity appeared to be induced by TGF-beta and IGF-1, the overall responsiveness of cartilage from aged mice to these growth factors appeared to be inhibitory. Moreover, their effects appeared to be limited to specific cell populations in the cartilage itself.

Journal Article↗
PubMed2000

Enhancement of toluidine blue staining by transforming growth factor-beta, insulin-like growth factor and growth hormone in the temporomandibular joint of aged mice.

Osteoarthritic lesions appear in the articular cartilage of the temporomandibular joint of mice aged 7 months and older. Reduced rate of proteoglycan (PG) synthesis leading to destruction of the articular cartilage was observed in this joint. The purpose of the present study was to test the ability of transforming growth factor-beta1 (TGF-beta1), insulin-like growth factor-1 (IGF-1) and growth hormone (GH) to induce PG synthesis in joint cartilage of aged animals and to compare it with the effect of interleukin-1alpha (IL-1alpha). Mandibular condyle explants from 18-month-old mice were cultured up to 72 h in serum-free medium, supplemented with IL-1alpha (TGF-beta1 (0.1-5.0 ng/ml), TGF-beta1 (1.0 ng/ml) + IGF-1 (2 ng/ml) or GH (10 ng/ml). The incorporation of (35)S-SO(4) into sulfated PG was tested. Cartilage samples were processed for histomorphometry using sections stained with 0.1% toluidine blue (TB), pH 1.8. Results indicated that in cultures supplemented (48 h) with either TGF-beta, TGF-beta + IGF-1 or with GH, an increased height and area of TB-positive staining as well as increased incorporation of (35)S-SO(4) into sulfated PG were observed. In contrast, the cytokine IL-1alpha exerted an inhibitory effect on TB staining and on (35)S-SO(4) incorporation. The present study demonstrated that in vitro supplementation of IL-1alpha to mandibular condyle cartilage reduced the height and area of TB staining and incorporation of (35)S-SO(4), whereas TGF-beta1, TGF-beta1 + IGF-1 or GH increased the height and area of TB staining and increased incorporation of (35)S-SO(4). The two parameters used to identify increased PG synthesis were shown to reveal similar results and were useful for studying the dynamic events taking place in cartilage destruction and repair in osteoarthritis.

Age Factors↗
PubMed1999

Delayed Detonation at a Single Point in Exploding White Dwarfs.

Delayed detonation in an exploding white dwarf, which propagates from an off-center transition point rather than from a spherical transition shell, is described and simulated. The differences between the results of two-dimensional simulations and the one-dimensional case are presented and discussed. The two-dimensional effects become significant in transition density below 3rho7, where the energetics, the production of Fe group elements, and the symmetry of the explosion are all affected. In the two-dimensional case, the explosion is less energetic and less Ni is produced in the detonation phase of the explosion. For low transition density, the reduction in Ni mass can reach 20%-30%. The asymmetry in abundances between regions close to the transition point and regions far from that point is large and could be a source of polarization patterns in the emitted light. We conclude that the spatial and temporal distribution of transition locations is an important parameter that must be included in delayed detonation models for Type Ia supernovae.

Journal Article↗
PubMed1999

Oxidative damage in rat tissue following excessive L-tryptophan and atherogenic diets.

Numerous reports were published on the connection between diets containing excessive L-tryptophan and the development of Eosinophilia Myalgia Syndrome. It has been also demonstrated that some cell functions depend on fatty acid composition which can result in increased lipid peroxidation in cells such as macrophages and other inflammatory cells. The purpose of the present study was to investigate the combined effects of an atherogenic diet enriched with tryptophan on lipid peroxidation in rats. 3-week-old CD-1 female rats were fed (3 weeks) control or atherogenic diets and the same diets supplemented with 0.4% or 1.0% L-tryptophan. Liver and skeletal muscle samples from all groups were taken for histology, autoradiography and for determination of lipid peroxidation. Infiltration of cells into fascia of muscle was observed following tryptophan or atherogenic diet consumption. However, no change in 3H-thymidine incorporation into DNA was observed by autoradiography. A significant increase of lipid peroxidation was detected in muscle following consumption of L-tryptophan-rich diets, with no significant difference from control in animals treated with atherogenic diets. Contrastly, a reduced lipid peroxidation was detected in liver of animals treated with excessive tryptophan as well as in animals fed on L-tryptophan and atherogenic diet or atherogenic diet alone. Our results indicated that excessive dietary tryptophan, when consumed with an atherogenic diet, increased lipid peroxidation in muscle but not in liver. Consumption of these feeding diets with or without supplementation of tryptophan resulted in reduced lipid peroxidation in muscle as well as in liver.

Animals↗
PubMed1999

Tryptophan toxicity--time and dose response in rats.

UNLABELLED: During the past decade L-tryptophan (Trp) ingestion have been associated with a multisystemic syndrome, known as eosinophilia myalgia syndrome (EMS). Even though an epidemic studies indicated that a contaminant, 1,1'-ethylidene-bis-L-tryptophan was involved in EMS, abnormalities in metabolism of Trp have been reported in other similar clinical syndromes such as carcinoid syndrome, scleroderma or eosinophilic fasciitis. The purpose of the study was to investigate the role of Trp or its metabolite, given in different dosing regimens in induction of tissue damage. METHOD: 3 months old female rats (Charles River CD-1) were fed for 3, 6, 12 weeks on a diet containing 20% protein diet derived from casein and supplemented with 1%, 2%, or 5% Trp. On the last week of feeding, half of the animals fed on a control diet and half of the animals fed on the Trp diet were injected with 2 injections of para-chlorophenyl alanine (p-CPA), a Trp hydroxylase inhibitor, 300 mg/kg i.p. followed by 3 injection of 100 mg/kg every alternate day. RESULTS: Body weight of rats fed higher levels of Trp increased slowly and injection of p-CPA induced loss in body weight. 2/6 of the animals treated with 1% Trp and 1/6 treated with 5% Trp for 3 weeks and 2/4 animals treated with 1% Trp and 1/4 treated with 5% Trp for 12 weeks died after injection of p-CPA. No mortality was detected in 1-5% Trp treated animals. Alopecia and skin changes were seen after p-CPA in 1-5% Trp treated animals. Increased amounts of connective tissue and induction of inflammatory cell proliferation were observed in lung, spleen and in gastrocnemia muscle of rats treated with higher dose of Trp for longer period. Induction of kynurenine pathway by injection of p-CPA caused more tissue damage. It is concluded that excessive Trp or elevation of its metabolites could play a role in amplifying some of pathological features of EMS. This pathological damage is further augmented by metabolites of the kynurenine pathway.

Alopecia↗
PubMed1997

Osteoarthritis in the temporo-mandibular joint (TMJ) of aged mice and the in vitro effect of TGF-beta 1 on cell proliferation, matrix synthesis, and alkaline phosphatase activity.

The temporo-mandibular joint of aged mice develops osteoarthritic (OA) degenerative lesions. Adult chondrocytes have a low rate of cell replication, and cartilage repair potential is very limited. One of the major problems in OA is the low rate of matrix synthesis and the inability of the chondrocytes to exceed the rate of matrix degradation. These combined factors lead to the overall destruction of the cartilage as seen in OA. Cartilage degradation is mediated by elevated proteolytic activity of enzymes. Among the enzymes degrading cartilage are the metalloproteinases, stromelysin and collagenase. Other proteinases that may potentially participate in matrix degradation are the lysosomal enzymes cathepsin B, D, and L, and acid phosphatase. On the other hand, alkaline phosphatase (ALP) is an enzyme that has been shown to be a marker for anabolic activity in skeletal tissues such as bone and cartilage. The cartilage of the mandibular condyle in the T-M-J from aged mice reveals OA lesions. An overall reduction of cell proliferation and sulfated proteoglycan synthesis has been also shown in this joint. In the present study the effects of hTGF-beta on the stimulation of DNA and sulfated GAG synthesis and ALP activity were studied. Mandibular condyle cartilage obtained from 12-month-old ICR male mice were cultured in BGJb serum-free medium for 24-72 hours, supplemented with 0.1-10 ng/ml hTGF-beta 1. 3H-thymidine and 35S-sulfate were added for the last 24 hours of the culture and their incorporation into DNA and sulfated GAGs respectively, as well as the activity of ALP, were determined. Results indicated that hTGF-beta 1 enhanced the incorporation of both 3H-thymidine and of 35S-sulfate into cartilage cultures of aged mice, and also induced ALP activity. It thus appeared that in OA degenerating articular cartilage, the chondrocytes could be stimulated in vitro to proliferate and to synthesize new matrix, thus indicating induced anabolic activity in the tissue.

Alkaline Phosphatase↗
PubMed1997

Comparison of in vitro response to growth hormone by chondrocytes from mandibular condyle cartilage of young and old mice.

In several aspects the features of aging resemble those of the state of growth hormone (GH) deficiency. Alterations of bone density and increased incidence of osteoporosis are some of the characteristics of aging that are similar to the findings in GH-deficient adults. Osteoarthritis (OA), a nonfatal condition predominating in old age, is characterized by the slowly progressive destruction of articular cartilage of joints. OA lesions are observed in the temporomandibular joint of ICR mice aged 7 months and older. The aim of the present study was to compare the response of chondrocytes from mandibular condyle cartilage of young and old mice to GH and to ascertain whether chondrocytes of old animals could still be stimulated to proliferate and to synthesize matrix components under the direct effect of GH in vitro. Mandibular condyles from young (3-month-old) and old (20-month-old) female ICR mice were cultured up to 72 hours in the presence of recombinant rat GH (0.1-100 ng/ml). 3H-Thymidine and 35S-sulfate were introduced during the last 24 hours of culture. Administration of GH appeared to increase only slightly the incorporation of 3H-thymidine in cartilage from young compared with the response in cartilage from old animals which was much more significant at 24 hours and 48 hours in culture. The same pattern was seen for the effect of GH on the incorporation of 35S-sulfate. Cartilage from young animals responded only slightly to GH, whereas a significant response was observed in cartilage from old animals after 24 and 48 hours in vitro. DNA contents were significantly elevated at all time intervals in both old and young animals, yet more significantly in cultures from old animals. In contrast, the activities of both alkaline and acid phosphatases were elevated at all time intervals in cultures from young animals, whereas no induction was observed in cultures from old animals. Tissue sections from cultures of old animals treated with GH (10 ng/ml, 48 hours) revealed atypical hypertrophic cells along the articular surface and also dark staining along the cartilage-bone interface. Exposure to tetracycline (10 mg/ml, 24 hours) resulted in an induced fluorescence, indicating enhanced mineralization in this region. Results of this study indicate that mandibular condyle cartilage from OA old mice responds in vitro to the addition of GH via anabolic activities of cell proliferation, sulfated proteoglycan synthesis, and possibly enhanced mineralization.

Aging↗
PubMed1997

Effects of transforming growth factor-beta 1 and interleukin-1 alpha on matrix synthesis in osteoarthritic cartilage of the temporo-mandibular joint in aged mice.

Osteoarthritic lesions were observed in the mandibular condyle cartilage of mice aged 7 months and older. These lesions appeared as fibrillations along the articular surface and were accompanied by reduced extracellular matrix synthesis and chondrocyte proliferation. Explants of mandibular condyle cartilage were cultured in serum-free BGJb medium supplemented with ascorbic acid (300 micrograms/ml), penicillin (100 U/ml) and streptomycin (100 micrograms/ml) for up to 72 h. Cultures were further supplemented with either hTGF-beta 1 (0.1-5.0 ng/ml) or human IL-1 alpha (40 U/ml). [3H]thymidine (2 microCi/ml) and [35S]SO4 (10 microCi/ml) were added to the culture medium for the last 24 h of culture and incorporation into DNA and sulfated proteoglycans, respectively, studied. The results indicated that protein and DNA contents, [3H]thymidine and [35S]SO4 incorporation, as well as the specific activity of alkaline phosphatase, were increased by TGF-beta 1. Addition of 1.0 or 5.0 ng/ml hTGF-beta 1 to the cultures for 48 h, had the most stimulatory effect on matrix synthesis and cell proliferation, whereas 0.1 ng/ml hTGF-beta 1 appeared to be inhibitory when compared to controls. Increased [35S]SO4 labeling of chondrocyte clusters was observed by autoradiography in tissue sections from cultures treated with TGF-beta 1 (1.0 and 5.0 ng/ml). In contrast, IL-1 alpha exerted inhibitory effects on cell proliferation and matrix synthesis. However, it induced the activity of acid phosphatase in these cultures. The results of the present study show that IL-1 alpha had catabolic effect on his tissue, while TGF-beta 1 enhanced proliferation and induced synthetic activity of the cartilage cells. Such action by TGF-beta suggests the existance of a possible repair process in osteoarthritic cartilage of the temporo-mandibular joint of aged mice.

Aging↗