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S Wientroub

Publications and source records attributed to S Wientroub.

At least 73 records · Page 4Linked to original sources
PubMed1990

Neutral endopeptidase (EC 3.4.24.11) is highly expressed on osteoblastic cells and other marrow stromal cell types.

A series of cultured mouse marrow stromal cell lines of different phenotype characteristics were examined for their neutral endopeptidase (NEP) activity using the highly selective chromophoric substrate of enzyme, 3-carboxypropanoyl-alanyl-alanyl-leucine 4-nitroanilide. All the cell lines tested contained appreciable amounts of NEP activity, but the cells expressing an osteoblastic phenotype, MBA-15, showed the high levels. Other non-stromal osteoblastic cell lines, MC-3T3-E1, ROS 17/2.8 cells derived from mouse long bone explants, were also rich in NEP. A four-fold stimulation of NEP activity was observed when certain MBA-15 clones were cultured in the presence of 1 alpha,25-dihydroxyvitamin D3. Since NEP is an effective cell-surface endopeptidase, it may play a role in the dynamics of bone formation, via interaction with biologically active polypeptides.

Amino Acid Sequence↗
PubMed1990

Influence of whole body irradiation and local shielding on matrix-induced endochondral bone differentiation.

Subcutaneous implantation of demineralized bone matrix into allogeneic rats induces endochondral bone formation. We have investigated the effects of irradiation on the sequelae of the interaction of collagenous matrix and mesenchymal cells and on cartilage and bone differentiation. Rats were irradiated in a vertical direction with a midline dose of 850 rad. Radiation entered the rats ventrally while a small area of the upper thorax was locally shielded. After irradiation, bone matrix was implanted in shielded and nonshielded sites, and the implants were studied at various stages. On day 3, [3H]thymidine incorporation, an index of cell proliferation, was inhibited by 70% in the nonshielded sites compared to nonirradiated control rats. The degree of inhibition (35%) was less pronounced in shielded sites. Furthermore, there was recovery of cell proliferation in the shielded sites as opposed to the nonshielded contralateral site. A similar pattern was observed on day 7 as assessed by 35SO4 incorporation into proteoglycans during chondrogenesis. Bone formation and mineralization were quantified on day 11 by alkaline phosphatase activity and 45Ca incorporation. In nonshielded sites, there was a 73% inhibition of alkaline phosphatase activity. In conclusion, radiation impaired progenitor cell proliferation which resulted in decreased cartilage and bone differentiation. These findings imply that local mesenchymal cells proliferate and differentiate into bone in response to implanted collagenous matrix.

Animals↗
PubMed1989

Bone marrow-derived stromal cell line expressing osteoblastic phenotype in vitro and osteogenic capacity in vivo.

Marrow stroma has been shown to have osteogenic potential. Here we report the characterization of a unique stromal cell line derived from mouse bone marrow (MBA-15), which expresses osteoblastic phenotype in vitro and forms bone in vivo. More than 70% of cells in culture were histochemically positive for alkaline phosphatase. The enzyme levels were enhanced threefold when cultures were treated with dexamethasone. Gel electrophoresis of [3H]-proline-labeled cultures showed that MBA-15 cells produced only type I collagen. These cells were responsive to PTH, as indicated by a 50-fold increase in intracellular cAMP. Prostaglandin E2, but not calcitonin, stimulated cAMP up to 70-fold. When cultures were grown to confluence and fed daily with ascorbic acid and beta-glycerophosphate, the cells formed a Von Kossa positive, thick extracellular matrix, shown to contain hydroxyapatite crystals. MBA-15 cells produced mineralized bone when implanted in diffusion chambers. These results indicate that the MBA-15 cell line possesses osteoblastic features in vitro and osteogenic capacity in vivo.

Alkaline Phosphatase↗
PubMed1989

Effect of vitamin D deficiency on macrophage and lymphocyte function in the rat.

Vitamin D deficiency has pronounced growth retardation effects on the skeletal system. Because the immune system has been implicated in the regulation of bone metabolism, we examined the effect of vitamin D deficiency on the functional development of immune function in a rachitic rat model. Rats deprived of vitamin D3 both in utero and in postnatal life (-/-) had significantly reduced thymocyte or splenocyte [3H]-thymidine incorporation to mitogens and decreased macrophage chemotaxis when compared with vitamin D3-sufficient rats (+/+). Rats that were deficient in vitamin D3 only during in utero development (-/+) or during postnatal life (+/-) tended to have [3H]thymidine incorporation levels that were intermediate to those of the -/- and +/+ group. Similarly, the chemotactic response of macrophages from the +/- and -/+ groups was intermediate to that of the -/- and +/+ group, except at high concentrations of C5a in which there was an overlap with the +/+ group. Interestingly, secretion of soluble mediators, including interleukin 2 by lymphocytes and interleukin 1 and PGE2 by macrophages, was unaffected by vitamin D deficiency. These results suggest that vitamin D3 is essential for the normal development of certain biological responses of lymphocytes and macrophages. Moreover, this rachitic rat model system will enable further evaluation of the role of vitamin D in the functional development of the cells of the immune system and their relationship to skeletal growth.

Animals↗
PubMed1988

Influence of irradiation on the osteoinductive potential of demineralized bone matrix.

Samples of demineralized bone matrix (DBM) were exposed to graduated doses of radiation (1-15 Megarad) (Mrad) utilizing a linear accelerator and then implanted into the thoracic region of Long-Evans rats. Subcutaneous implantation of DBM into allogenic rats induces endochondral bone. In response to matrix implantation, a cascade of events ensues; mesenchymal cell proliferation on day 3 postimplantation, chondrogenesis on day 7, calcification of the cartilagenous matrix and chondrolysis on day 9, and osteogenesis on day 11 resulting in formation of an ossicle containing active hemopoietic tissue. Bone formation was assessed by measuring alkaline phosphatase activity, the rate of mineralization was determined by measuring 45Ca incorporation to bone mineral, and 40Ca content measured the extent of mineralization; acid phosphatase activity was used as a parameter for bone resorption. The dose of radiation (2.5 Mrad) currently used by bone banks for sterilization of bone tissue did not destroy the bone induction properties of DBM. Furthermore, radiation of 3-5 Mrad even enhanced bone induction, insofar as it produced more bone at the same interval of time than was obtained from unirradiated control samples. None of the radiation doses used in these experiments abolished bone induction, although the response induced by matrix irradiated with doses higher than 5 Mrad was delayed.

Acid Phosphatase↗
PubMed1987

Noncollagenous bone proteins in experimental rickets in the rat.

Rats were raised in the absence of vitamin D in utero and throughout post-fetal life and neither 1,25-dihydroxyvitamin D3 nor related metabolites were detected in serums. No changes were observed in the relative amount of extractable noncollagenous bone proteins (NCP) in rachitic compared to vitamin-D-repleted animals. As expected, the relative levels of the mineral-bound, serum-derived albumin and alpha 2HS glycoprotein were unaffected in bones of rachitic animals. Interestingly, the vitamin D deficiency also did not have dramatic effects on several bone cell-derived noncollagenous proteins including: bone proteoglycans I & II, bone sialoprotein II osteonectin, and osteocalcin. In contrast to the proteoglycans, the bone sialoprotein II and osteonectin were found in the nonmineral compartment of the rachitic animals, presumably bound to the wide osteoid seam.

Animals↗
PubMed1987

The dichotomy in the effects of 1,25 dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 on bone gamma-carboxyglutamic acid-containing protein in serum and bone in vitamin D-deficient rats.

Vitamin D-deficient, second generation, rachitic rats showed significant decrease in bone Gla protein (BGP) levels in circulation and in the skeleton. 1,25 dehydroxyvitamin D3 (1,25(OH)2D3) exhibited the most potent influence on serum BGP levels in a dose-dependent manner. At a dose 25 ng/100 g body weight 1,25(OH)2D3 showed a cumulative effect, i.e., the longer the treatment, the more circulating BGP was detected. 24,25 dehydroxyvitamin D3 (24,25(OH)2D3) at the same doses did not show similar effect on the serum BGP levels, regardless of the serum calcium levels. Bone BGP levels assayed at various sites representing endochondral and intramembranous ossification demonstrated an opposite pattern. 1,25(OH)2D3 administration was not sufficient to restore bone BGP levels to normalcy, whereas in animals treated with 24,25(OH)2D3, bone BGP and calcium levels were significantly higher than control (Vitamin D3-repleted) levels. The present results can be explained by the dual action of 1,25(OH)2D3 on both synthesis and release of BGP by bone turnover, whereas 24,25(OH)2D3 stimulates synthesis and accumulation of BGP in bone. These observations imply that caution is required in the interpretation of clinical data based solely on serum BGP determination.

24,25-Dihydroxyvitamin D 3↗
PubMed1987

Milk protein synthesis by mammary glands of vitamin D-deficient mice.

Mammary glands from second generation vitamin D-deficient mice and rats were examined for their ability to make the major milk proteins, casein and alpha-lactalbumin, both in vivo and in vitro. The glands from the rachitic animals were morphologically indistinguishable from those of age-matched controls. When placed in explant culture, glands from vitamin D-deficient mice and rats underwent DNA synthesis at a rate comparable to that of glands from the vitamin D-replete controls. However, the hormonally induced synthesis of casein and alpha-lactalbumin was significantly reduced in explants of glands from rachitic vs. control animals. The reduction in casein-synthesizing ability by mouse mammary gland explants was not reversed by the addition of 10(-8) or 10(-6) M 1,25-dihydroxycholecalciferol to the culture medium, but could be reversed by pretreating the vitamin D-deficient mice with the D metabolite in vivo for 10 days before the onset of culture. The decrease in milk protein synthesis in culture is paralleled in vivo by a decrease in milk protein content in the milk and lactating mammary glands of vitamin D-deficient mice and rats. Both in vivo and in vitro, it is the two highest mol wt caseins that are most affected by the lack of vitamin D in the diet. These data suggest that vitamin D does not play a fundamental role in growth and morphological development of the normal mammary gland, but, rather, it is important in maintenance of full hormonally induced functional differentiation of the mature gland.

Animals↗
PubMed1987

Residual adduction of the forefoot. A review of the Turco procedure for congenital club foot.

Forty-four feet in 28 children previously treated by a one-stage posteromedial release operation (the Turco procedure) were reviewed clinically and radiologically to determine the cause of residual adduction of the forefoot. In 21 clinically adducted feet (48%) the main cause of residual deformity was metatarsus varus alone or metatarsus varus in spite of talonavicular overcorrection; in five feet the cause was talonavicular subluxation. There was no residual adduction in 23 feet (52%) but only 12 had normal radiographic measurements. In the remaining feet, various forms of spurious correction of metatarsus varus and talonavicular subluxation or both were seen, resulting in normal-looking feet. Recession of the origin of abductor hallucis and release of the short plantar muscles and fascia at the time of posteromedial release is recommended. The forefoot adduction was satisfactorily corrected in 91% of the feet subsequently operated on using this modified procedure.

Child↗
PubMed1987

Development of the olecranon bursa. An anatomic cadaver study.

Anatomic dissection of the elbows of 63 cadavers selected at random were performed in an attempt to find out whether the incidental disparity of olecranon bursitis between children and adults might be explained by anatomic differences. The volume of the bursae was determined by syringes used for methylene blue injections. There were no olecranon bursae in children under the age of 7 years; the volume of the bursae increased with age; and the bursa was usually larger on the right, i.e., the common dominant side. The formation of the bursae in late childhood can explain the low incidence of olecranon bursitis in children.

Adolescent↗
PubMed1987

Seasonal variation in paired maternal-newborn serum 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations in Israel.

Seasonal changes were observed in the vitamin D status of mothers and their newly born infants in sunny Israel. Maternal and newborn serum levels of 25-hydroxyvitamin D (25-OHD) were lower (less than 0.01) in March-April (n = 45 pairs), than in September-October (n = 33 pairs). Parallel seasonal changes were also found in serum 24,25-dihydroxyvitamin D [24, 25-(OH)2D] concentrations. In the spring, 20% of the mothers and 40% of their infants had vitamin D deficiency or borderline serum 25-OHD levels. In the autumn, in contrast, none of the mothers and only one newborn were vitamin D-deficient, and one mother and two newborns had borderline serum 25-OHD levels. The results demonstrate that even in Mediterranean climates there are seasonal changes in maternal vitamin D status, which have a significant effect on the serum levels of vitamin D metabolites in their newborn infants. This raises the question as to whether vitamin D supplements should be given to pregnant women in Israel, at least during the winter.

24,25-Dihydroxyvitamin D 3↗
PubMed1987

Biologic principles of bone induction.

This article provides a concise review of bone induction. Bone induction by demineralized bone matrix is a multistep cascade. The purification and elucidation of the chemistry of osteogens will improve bone grafting methods.

Alkaline Phosphatase↗
PubMed1986

The effect of vitamin D deficiency on rat bone lipid composition.

Vitamin D and phosphate deficiency has been shown previously to result in an accumulation of calcium acidic phospholipid phosphate complexes in the epiphysis of immature rats and to increase the cholesterol and decrease the lysophosphatide content throughout bone. To define the effects of vitamin D deficiency and those of combined vitamin D and phosphate deficiency, the lipid composition of the bones of second generation rachitic rats, raised on a diet that was vitamin D deficient was compared to that of normal animals fed a vitamin D-repleted diet and to previously studied vitamin D and phosphate-deficient rats. Animals raised on the vitamin D-deficient diet in utero and during postfetal life were serologically quite different from controls. These animals were significantly hypocalcemic and had no detectable vitamin D metabolites. Similar to the previously studied phosphate-deficient rachitic animals, the vitamin D-deficient animals had significantly elevated total lipid contents (weight percent lipid per demineralized dry weight) throughout their bones as compared to controls (epimetaphysis 9.6 vs 6.7 (P less than or equal to 0.03), diaphysis 6 vs 2 (P less than or equal to 0.01), calvaria 6.1 vs 2.4 (P less than or equal to 0.002). Similar to the vitamin D and phosphate-deficient animals, the second generation vitamin D-deficient rat bones had elevated cholesterol and reduced lysophosphatide contents. Complexed acidic phospholipids were not significantly elevated in the vitamin D-deficient animal bones. The data suggest that the lipid changes seen in these animals are due to vitamin D deficiency and not to phosphate deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Extracellular matrix proteins involved in bone induction are vitamin D dependent.

Subcutaneous implantation of demineralized diaphyseal bone matrix into allogeneic rats results in local formation of cartilage and bone. However, implantation of demineralized bone matrix obtained from rachitic rats did not induce bone. Rachitic bone matrix was therefore dissociatively extracted with 4 M guanidine HCl and then reconstituted with an inactive collagenous residue of control as carrier. Such reconstituted materials also lacked bone inductive potential. On the other hand, reconstitution of guanidine HCl extracts of control bone matrix with inactive vitamin D deficient matrix did result in bone induction. Partial purification (fractions containing proteins (less than 50,000 daltons) of the guanidine HCl extract from rachitic rats on Sepharose CL-6B followed by reconstitution with inactive collagenous residues resulted in a weak (25% of control) inductive response. These observations imply that bone inductive proteins are vitamin D dependent and are reduced in matrix obtained from rachitic rats.

Animals↗
PubMed1984

Establishment of the hematopoietic microenvironment in the marrow of matrix-induced endochondral bone.

Implantation of demineralized diaphyseal bone matrix (DBM) into subcutaneous sites in allogeneic Long-Evans rats results in new endochondral bone formation accompanied by hematopoietic bone marrow differentiation in the newly formed ossicles. In the present study, we investigated the relationship between the time of appearance of hematopoietic stem cells (CFU-S) and those of certain postulated elements of the hematopoietic microenvironment, i.e., fibroblast colony-forming cells (CFC-F), colony-stimulating factors (CSF), and collagen types. CFU-S were first detected at 16 days' postimplantation in the developing ossicle. Their numbers increased exponentially until day 24, decreased slightly between days 27 and 33, and then slowly increased in number again until day 36. CFC-F were present at day 10, and their numbers increased exponentially until day 15, decreased dramatically until day 24, and then remained constant till day 35. Thus, the transient growth of CFC-F preceded the appearance and growth of CFU-S in the ossicle by two or three days.

Animals↗
PubMed1983

Changes in tissue concentration of prostaglandins during endochondral bone differentiation.

Prostaglandins are known to be involved in bone metabolism as evidenced by the ability of PGE2 to induce bone resorption. It was, therefore, of interest to determine if there was an association of specific prostaglandin metabolites with the various stages of developing bone by utilizing the matrix-induced endochondral bone formation system. During mesenchymal cell proliferation a peak of endogenous thromboxane B2 was detected. In the subsequent stages of chondrogenesis and chondrolysis PGF2 alpha was in high concentration, whereas during bone formation PGE2, 6-Keto-PGF1 alpha and thromboxane B2 were elevated. These changes in the peak levels of the various prostaglandin metabolites may reflect differences in the cell populations and function associated with various stages of endochondral bone formation.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Tibial dysplasia. A study of the anatomy.

Three amputated legs with tibial dysplasia were studied by radiography, arteriography and anatomical dissection. The radiographic appearances were the same as the Type 1b tibial dysplasia described by Jones, Barnes and Lloyd-Roberts (1978) in that the tibiae were absent but the lower femoral epiphyses were normal. However, our anatomical findings differed from those of Jones et al. since no bony or cartilaginous anlage of the proximal tibia was found in any of the three legs. The pattern of vascular anomaly was identical in the three legs and similar to the findings of Hootnick et al. (1980) in congenital short fibula. Congenital fusion of the subtalar joint was a constant finding. These results support the hypothesis that the arterial and skeletal systems are vulnerable to a teratogenic insult in the fifth week of embryonic life. The bony and arterial anomalies should be borne in mind by the surgeon attempting reconstructive surgery for this condition.

Angiography↗