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PubMed2002

Long-term culture of primary human hepatocytes with preservation of proliferative capacity and differentiated functions.

BACKGROUND: The aim of this study was to develop a suitable method for the prolonged culture and maintenance of human hepatocytes with preservation of both proliferative capacity and differentiated functions. MATERIALS AND METHODS: Primary human hepatocytes were isolated from small pieces of liver tissue obtained from 15 patients who underwent hepatic resection. Hepatocytes were cultured in keratinocyte-stimulating factor medium supplemented with 10% human serum, 10 mM nicotinamide, 10 ng/ml epidermal growth factor, 0.5 microg/ml insulin, 10(-7) M dexamethasone, and antibiotics. Hepatic differentiation and function were analyzed by immunocytochemistry, Western blot, ELISA, lidocaine metabolism, and urea synthesis. Ultrastructural analysis of cultured hepatocytes was performed by electron microscopy. RESULTS: Many primary hepatocytes were maintained for more than 56 days. Hepatocytes proliferated during the initial 14 days, and bromodeoxyuridine labeling indices were 15.2, 12.2, and 6.2% at days 5, 10, and 15, respectively. Electron micrographs of the hepatocytes at day 28 demonstrated numerous mitochondria, rough endoplasmic reticulum, large peroxisomes, and glycogen granules. Albumin secretion increased for the first 14 days and then gradually decreased thereafter but was maintained at levels greater than 2 microg/ml/h until day 56. alpha(1)-Antitrypsin, alpha(1)-antichymotrypsin, and ceruloplasmin production was also observed at day 56, while lidocaine metabolism and urea synthesis were maintained for a long time. CONCLUSION: This hepatocyte culture method facilitates the prolonged culture of primary human hepatocytes with preservation of hepatocyte differentiation, function, and proliferative capacity.

Adolescent↗

PubMed1991

CCl4 cirrhosis in rats: irreversible histological changes and differentiated functional impairment.

Cirrhosis of the rat liver was induced by a 12 week individualized CCl4/phenobarbital treatment. After treatment, all surviving animals (81%) showed cirrhosis of the liver. The cirrhosis induced was irreversible when evaluated 24 weeks after cessation of treatment. Quantitative liver function measurements were reduced in a differentiated manner. Ranked according to the most pronounced changes they are: capacity of urea-N synthesis (CUNS), galactose elimination capacity (GEC) and antipyrine clearance (APC). Hepatic glutathione concentrations were only slightly decreased after the CCl4 treatment. It is possible to produce a high incidence of irreversible cirrhosis with differentiated functional impairment in the rat.

Animals↗

PubMed2000

Assessing differential functioning in a satisfaction scale.

In this study, an item response theory-based differential functioning of items and tests (DFIT) framework (N. S. Raju, W. J. van der Linden, & P. F. Fleer, 1995) was applied to a Likert-type scale. Several differential item functioning (DIF) analyses compared the item characteristics of a 10-item satisfaction scale for Black and White examinees and for female and male examinees. F. M. Lord's (1980) chi-square and the extended signed area (SA) measures were also used. The results showed that the DFIT indices consistently performed in the expected manner. The results from Lord's chi-square and the SA procedures were somewhat varied across comparisons. A discussion of these results along with an illustration of an item with significant DIF and suggestions for future DIF research are presented.

Black or African American↗

PubMed2000

Functional differentiation in the human auditory and language areas revealed by a dichotic listening task.

The human auditory cortex plays a special role in speech recognition. It is therefore necessary to clarify the functional roles of individual auditory areas. We applied functional magnetic resonance imaging (fMRI) to examine cortical responses to speech sounds, which were presented under the dichotic and diotic (binaural) listening conditions. We found two different response patterns in multiple auditory areas and language-related areas. In the auditory cortex, the medial portion of the secondary auditory area (A2), as well as a part of the planum temporale (PT) and the superior temporal gyrus and sulcus (ST), showed greater responses under the dichotic condition than under the diotic condition. This dichotic selectivity may reflect acoustic differences and attention-related factors such as spatial attention and selective attention to targets. In contrast, other parts of the auditory cortex showed comparable responses to the dichotic and diotic conditions. We found similar functional differentiation in the inferior frontal (IF) cortex. These results suggest that multiple auditory and language areas may play a pivotal role in integrating the functional differentiation for speech recognition.

Acoustic Stimulation↗

PubMed1992

The autocrine role of tumor necrosis factor in the proliferation and functional differentiation of human lymphokine-activated T killer cells (T-LAK) in vitro.

The autocrine role of tumor necrosis factor alpha (TNF) in the proliferation and functional differentiation of human lymphokine-activated T-killer cells (T-LAK) in vitro was investigated. Human peripheral blood lymphocytes initially stimulated with IL-2 and phytohemagglutinin-P (PHA) for 48 h will proliferate for long periods in vitro in the presence of IL-2. These T-LAK cells have been shown to be 95% CD3 positive. Employing ELISA techniques, greater than 500 pg/ml of TNF was found to be released in the supernatants of these cells during the first 5 days of culture. However, the levels dropped to 100-200 pg/ml by days 7-10. T-LAK cells grown from days 7 to 10 in the presence of IL-2 and rabbit anti-TNF were significantly growth inhibited (up to 23%). The cytolytic activity of T-LAK cells grown from days 0 to 7 in the presence of anti-TNF was also decreased (up to 75%). Phenotypic analysis of these anti-TNF treated T-LAK cells revealed a decrease in CD8 expression (up to 12%) and increase in CD4 expression (up to 27%) when compared with control cells. The data suggest that TNF has a regulatory role in the growth and functional differentiation of these human T-LAK cells.

CD4 Antigens↗

PubMed1991

Effects of ageing on the growth and differentiated function of transfected human thyrocytes.

Senescence in primary cultures of mammalian cells is characterised by cessation of growth after a number of cell divisions; this may be associated with loss of some differentiated functions. Recent studies on bovine adrenocortical cells have suggested that expression of simian virus-40 (SV40) early region in these cells may prevent phenotypic losses due to senescence. We report here data on growth and differentiated function of two human thyrocyte cell lines (SGHTL-34 and -45) generated by the transfection of primary thyrocytes with the plasmid pSV3neo which contains the SV40 early region. Growth was assessed by fluorometric DNA estimations and calculation of cell population doubling time; function was assessed by binding studies using 125I-bovine thyrotrophin (TSH) and measurement of cyclic adenosine 3',5'-monophosphate (cAMP) response to stimulation with TSH, forskolin and cholera toxin. After 3-12 months in stable culture there was a gradual increase in the doubling time of both cell lines over a 3-month period (SGHTL-34 cells, early 34.5 +/- 4.5 h, late 301 +/- 111.6 h; SGHTL-45 cells, early 53.4 +/- 4.4 h, late 148.3 +/- 26.3 h; mean +/- SEM). Scatchard analysis demonstrated a loss of the high affinity TSH receptor over the same time period. The increase in cAMP in response to 1000 microU/ml TSH declined until the cells became unresponsive (SGHTL-34 early, cAMP 10.3 +/- 0.7 pmol/well; late, cAMP -0.4 +/- 0.3 pmol/well; SGHTL-45 early, cAMP 11.3 +/- 1.1 pmol/well, late, cAMP 0.3 +/- 0.1 pmol/well). The cAMP responses to forskolin and cholera toxin were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMed1985

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate enhances the long-term maintenance of pancreatic islet B cell differentiated function in tissue culture.

A study was undertaken to examine the effects of the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, on pancreatic islet B cell differentiated function and number. Islets from 3-day-old rats were maintained in tissue culture for up to 30 days with or without the addition of the phorbol ester. Changes in the insulin content of the media and tissue were determined at 48 hr and weekly intervals, respectively, using radioimmunoassay. The 30-day cumulative output of insulin into the medium was increased almost 2-fold and the tissue insulin content was increased 4-fold by the phorbol ester. Counts of cell smears processed for the immunocytochemical localization of insulin indicated no effect on the total numbers of B cells or non-B cells in either control or treated cultures. This enhanced maintenance of islet B cell differentiated function by 12-O-tetradecanoylphorbol-13-acetate suggests that pancreatic islets may be a useful model with which to study the mechanisms of action of this and other tumor-promoters.

Animals↗

PubMedDate not supplied

Hormonal induction of functional differentiation and mammary-derived growth inhibitor expression in cultured mouse mammary gland explants.

A method for the cultivation of organ explants from abdominal mammary glands of virgin mice has been established. In a serum-free medium containing aldosterone, prolactin, insulin, and cortisol (APIH medium) mammary gland development was documented by lobuloalveolar morphogenesis. The hormonal requirements for in vitro expression of beta-casein and of the mammary-derived growth inhibitor (MDGI) were tested. To this end, a full length cDNA coding for mouse MDGI was prepared displaying strong homologies to a mouse heart fatty acid binding protein, which is also expressed in the mammary gland. MDGI and beta-casein transcripts were found to be absent in the mammary tissue from primed virgin mice, and were induced upon culture of mammary explants in the APIH medium. An immunohistochemical analysis with specific antibodies against MDGI and casein revealed a different pattern of expression for the two proteins. In the APIH medium, MDGI was expressed mainly in differentiating alveolar cells of the lobuloalveolar structures, whereas beta-casein was present in both ductules and alveoli. The relationship between functional differentiation and MDGI expression was further studied in explants from glands of late-pregnant mice. At this stage of development, MDGI is found both in ducts and in alveoli. If explants were cultured with epidermal growth factor (EGF) and insulin, the lobuloalveolar structure was still present, whereas MDGI disappeared. Reinduction of MDGI expression was achieved by subsequent PIH treatment. Independent on developmental stage, EGF strongly inhibits MDGI mRNA expression. It is concluded that MDGI-expression is associated with functional differentiation in the normal gland.

Aldosterone↗

PubMed1994

Phorbol 12-myristate 13-acetate stimulates proliferation and ductal morphogenesis and inhibits functional differentiation of normal rat mammary epithelial cells in primary culture.

The effect of the tumor promoter phorbol 12-myristate 13-acetate (PMA) on proliferation and differentiation of normal mammary epithelial cells from 50-day-old virgin rats was investigated using a model system that allows for full morphological and functional development of the cells. In this model, mammary epithelial cells are grown within a reconstituted basement membrane in a defined serum-free medium. PMA at a concentration of 10(-6) M effected translocation of protein kinase C from cytosol to membrane. At the same concentration, it stimulated cell proliferation both in the presence and absence of EGF, and this stimulation was observed even when PMA exposure was limited to 15 min at the time of each media change. In contrast to the effect on proliferation, PMA at concentrations of 10(-7) and 10(-6) M inhibited functional differentiation as assessed by casein accumulation. Phorbol 12,13-dibutyrate at 10(-6) M also stimulated proliferation and inhibited casein accumulation and was more effective than PMA in both cases. In contrast, the nonactive tumor promoter 4-alpha PMA had no effect on either proliferation or differentiation. One of the most striking effects of PMA was its ability to stimulate an atypical ductal morphogenesis, as manifested by the formation of intricate web-like colonies, and to inhibit the development of the well-differentiated alveolar-like multilobular colonies. PMA was also shown to completely suppress the growth of the squamous-like colonies that develop when EGF is absent or deficient. These effects of phorbol esters in mammary epithelial cells to stimulate proliferation, inhibit functional differentiation, and stimulate the development of ductal colonies are consistent with the suggestion that the signal transduction pathways evoked by PMA could act to stimulate the growth of initiated cells or render normal cells more sensitive to carcinogen.

Animals↗

PubMed1999

Oestradiol stimulates morphological and functional differentiation of human villous cytotrophoblast.

Trophoblast differentiation is a complex process involving interactions of cytotrophoblastic cells with their evolutive milieu. During pregnancy, the feto-placental unit produces large amounts of steroids. Progesterone and oestradiol are increasingly produced when the syncytiotrophoblast is highly differentiated. Furthermore, receptors to these hormones are expressed by the trophoblast. This led us to test the hypothesis that steroid production could affect the morphological and functional differentiation of the trophoblast during gestation. The fusion of cytotrophoblastic cells into syncytiotrophoblast was assessed using fluorescence recovery after photobleaching for gap junctional communication analysis (gap-FRAP), desmoplakin immunostaining and connexin 43 expression. In parallel, functional differentiation was assessed by beta-human chorionic gonadotrophin (betahCG) production and human chorionic somatomammotropin (hCS) expression analysis. The presence of oestradiol, 1 microm, increased the percentage of coupled cells (3. 8-fold), connexin 43 expression and stimulated the syncytium formation. In parallel, oestradiol (1, 3 and 5 microm) induced a significant increase in the daily hCG production. The steroid action was specific, as the stimulatory effects were inhibited by tamoxifen. Oestradiol also stimulated hCS expression (51 per cent compared to control after 3 days). As trophoblastic differentiation is specifically stimulated by hCG, oestradiol could act via the stimulation of hCG production or via a direct action. In the presence of an efficient concentration of hCG antibody, oestradiol still stimulated hCS expression, suggesting a self-sufficient effect of the steroid. Physiological concentrations of progesterone were ineffective in modulating trophoblast differentiation. In conclusion, oestradiol could be implicated in the maturation and aging of the trophoblast.

Cell Differentiation↗

PubMed1987

Influence of some dietary chemopreventive agents on the expression of functional differentiation of the mouse mammary gland in vitro.

The purpose of the present studies was to determine the influence of the chemopreventive agents selenium, 4-(hydroxyphenyl)-retinamide (4-HPR) and beta-carotene, on functional differentiation (lactogenesis) of the mouse mammary gland cells. The hormone-induced expression of the milk-protein genes, beta-casein, epsilon-casein and the whey acidic protein (WAP) was used as molecular marker of differentiation of the mammary cells in organ culture medium containing insulin, prolactin, aldosterone and hydrocortisone. Quantitative determination of the cellular concentration of the respective mRNA was ascertained by molecular hybridization of RNA to the specific cloned cDNA probes using both the solution and the filter hybridization methods. Selenium at 100 nm concentration caused a pronounced inhibition of accumulation of the respective mRNAs. The retinoid, 4-HPR, also caused a dose-dependent inhibition of expression of these mRNA sequences. In contrast, concentrations of the 3 mRNAs in beta-carotene-treated glands remained similar to those observed in glands cultured in medium containing the hormones and hexane (the latter being the solvent for beta-carotene). The significant antagonistic action of selenium and 4-HPR, however, was reversible after removal of the chemicals from the culture medium. Thus, among the 3 chemicals tested, selenium and retinoid can cause an adverse effect on functional differentiation (lactogenesis) of the mammary cells. This inhibitory effect, however, was reversible. beta-Carotene, on the other hand, caused no apparent antagonistic effect on expression of the milk-protein genes in the isolated whole mammary organ in culture.

Actins↗

PubMed1999

Functional differentiation of medial temporal and frontal regions involved in processing novel and familiar words: an fMRI study.

Results of recent functional magnetic resonance imaging (fMRI) studies of memory are not entirely consistent with lesion studies. Furthermore, although imaging probes have identified neural systems associated with processing novel visual episodic information, auditory verbal memory using a novel/familiar paradigm has not yet been examined. To address this gap, fMRI was used to compare the haemodynamic response when listening to recently learned and novel words. Sixteen healthy adults (6 male, 10 female) learned a 10-item word list to 100% criterion, approximately 1 h before functional scanning. During echo-planar imaging, subjects passively listened to a string of words presented at 6-s intervals. Previously learned words were interspersed pseudo-randomly between novel words. Mean scans corresponding to each word type were analysed with a random-effects model using statistical parametric mapping (SPM96). Familiar (learned) words activated the right prefrontal cortex, posterior left parahippocampal gyrus, left medial parietal cortex and right superior temporal gyrus. Novel words activated the anterior left hippocampal region. The results for the familiar words were similar to those found in other functional imaging studies of recognition and retrieval and implicate the right dorsolateral prefrontal and left posterior medial temporal lobe (MTL) regions. The results for novel words require replication, but are consistent with the substantial lesion and PET literature implicating the anterior MTL as a critical site for processing novel episodic information, presumably to permit encoding. Together, these results provide evidence for an anterior-posterior functional differentiation within the MTL in processing novel and familiar verbal information. The differentiation of MTL functions that was obtained is consistent with a large body of PET activation studies but is unique among fMRI studies, which to date have differed from results with PET. Further, the finding of left MTL lateralization is consistent with lesion-based material-specific models of memory.

Adult↗

PubMed1999

Induction of functional differentiation and growth inhibition in vitro of canine osteosarcoma by 22-oxacalcitriol, calcitriol and all-trans retinoic acid.

The effects of 22-oxacalcitriol (OCT), calcitriol and all-trans retinoic acid (ATRA) on the induction of functional differentiation and growth inhibition of the canine osteosarcoma cell line POS were investigated in vitro via bone differentiation markers and proliferation assays, respectively. The intracellular alkaline phosphatase (ALP) activity and the gamma-carboxyglutamic acid osteocalcin (GLA-OC) and procollagen type I C peptide (PIP) production were used as markers of differentiation. Treatment with 10(-8) M concentrations of all drugs for 72 h significantly inhibited growth (P < 0.0001) and increased ALP activity and GLA-OC and PIP production in POS. OCT, calcitriol and ATRA significantly increased the: ALP activity from 1.58 +/- 0.14 mumol/min/mg protein (mean +/- SD; control) to 2.50 +/- 0.09 (P < 0.0001), 2.30 +/- 0.14 (P < 0.0001) and 2.00 +/- 0.14 (P = 0.0008), respectively; GLA-OC production from 0.71 +/- 0.01 ng/ml (control) to 2.87 +/- 0.01 (P < 0.0001), 2.87 +/- 0.11 (P < 0.0001) and 1.36 +/- 0.06 (P < 0.0001), respectively; and PIP production from 433.91 +/- 23.29 ng/ml (control) to 536.54 +/- 15.46 (P = 0.0002), 497.06 +/- 1.99 (P = 0.0028) and 481.66 +/- 0.01 (P = 0.0104), respectively. This study demonstrated that treatment with these drugs induced a phenotypic maturation of POS cells into cells that exhibit the properties of functionally mature bone cells with parallel growth inhibition. The effects of these drugs on functional differentiation may be useful to complement the progression of a normal osteogenic differentiation process in the sarcoma.

Alkaline Phosphatase↗

PubMed2001

Morphological and functional differentiation of human thyroid cells in collagen gel culture.

OBJECTIVE: Cultured human thyroid cells in collagen gel culture were examined on cell morphology and the production of thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4) which are components of functional differentiation. METHODS: Thyroid cells obtained from normal human thyroid tissues (four cases), follicular adenoma tissues (three cases), papillary carcinoma tissues (three cases), and follicular carcinoma tissue (one case), were cultured in collagen gel. Then these cultured cells were observed on cellular morphology and production of Tg, T3 and T4. Moreover, changes in morphological characteristics and production of Tg, T3 and T4 induced by addition of thyroid stimulating hormone (TSH) and epidermal growth factor (EGF) to medium in collagen gel culture were determined. RESULTS: Normal and tumor cells in collagen gel culture formed colonies and follicles with Tg production, similar to in vivo-like three-dimensional cellular structures and functions. Normal thyroid cells stimulated TSH induced more Tg and produced morphological changes, i.e. enlarged follicular lumens and increased the height of follicular cells, but did not promote cell proliferation. Reversely, normal thyroid cells stimulated with EGF promoted cell proliferation, but did not change morphological findings and did not increase production of Tg, T3 and T4. CONCLUSIONS: These findings suggest that collagen gel culture is useful for observing the effects of stimulation by cell growth factor on the morphological and functional differentiation of human thyroid cells.

Cell Differentiation↗

PubMed1983

Expression of differentiated function by hepatocytes in primary culture: variable effects of glucagon and insulin on gluconeogenesis during cell growth.

Hormonal effects on gluconeogenesis from lactate were studied during the growth cycle of adult rat parenchyma liver cells using a primary monolayer culture system previously described [25]. Basal and glucagon-stimulated gluconeogenic ability were found to decline rapidly during log phase, insulin-stimulated growth. A progressive recovery of gluconeogenesis activity was observed after cell division subsided. Rates of lactate-gluconeogenesis were found also to decline in the absence of prior insulin exposure. This decline was not as rapid as the loss observed in cells cultured with insulin. However, in insulin-deficient cultures gluconeogenesis was completely abolished after 12 days and did not reelevate with further incubation unless cells were washed and exposed to glucagon. Decreasing growth rates of insulin-supplemented cultures by decreasing serum concentrations resulted in comparatively higher gluconeogenic activity. The results presented here are consistent with previous observations of hepatic parenchymal expression of 'differentiated function' during cellular growth phases in culture (i.e., differentiated functions are generally lost during rapid growth and regained as cells become quiescent). The present study, however, presents unexpected effects of insulin on the apparent growth-state dependent gluconeogenic recovery. Our data imply that although insulin has long been known to inhibit gluconeogenesis, its presence in culture may facilitate long-term basal maintenance of gluconeogenic enzyme activity. Insulin also functions as a growth factor whose initial mitogenic effect correlates with decreased gluconeogenic function. These changes show no simple or predictive correlation with cyclic nucleotide metabolism.

Animals↗

PubMed1994

Involvement of epidermal growth factor (EGF)/EGF receptor autocrine and paracrine mechanism in human trophoblast cells: functional differentiation in vitro.

We have studied the expression of epidermal growth factor (EGF) and EGF receptors (EGF-R) in isolated human trophoblast cells at various stages of differentiation and also the biological significance of the EGF/EGF-R autocrine and paracrine mechanism. Cytotrophoblast cells were isolated from human placental tissues of 6-9 weeks of gestation. Trophoblast cells underwent morphological and functional differentiation during in vitro culture. The expression of EGF and EGF-R protein and mRNA was studied in trophoblast cells cultured for 0-5 days, using immunocytochemical staining, and reverse transcription and polymerase chain reaction. Monoclonal antibodies (mAbs) against EGF and EGF-R showed specific staining in trophoblast cells at all stages of differentiation. Both EGF and EGF-R gene transcripts were detected in RNA samples isolated from trophoblast cells at all stages. These data suggest the presence of an EGF/EGF-R autocrine and paracrine mechanism in human trophoblast cells. Next, we examined the biological significance of this mechanism on trophoblast cell differentiation in vitro. EGF added to the culture medium significantly increased human chorionic gonadotrophin-beta (hCG-beta) secretion and, more importantly, anti-EGF neutralizing mAbs significantly reduced both hCG-beta and human placental lactogen secretion from trophoblast cells in culture. All these results suggest that human trophoblast cells express both EGF and EGF-R, and that EGF may play an important role in the functional differentiation of human trophoblast cells.

Base Sequence↗

PubMed2004

Examining the effects of differential item (functioning and differential) test functioning on selection decisions: when are statistically significant effects practically important?

Item response theory differential test functioning (DTP) methods are often used to address issues in personnel selection, but the results are frequently difficult to interpret because statistically significant findings may have little practical importance. In this article, the authors proposed 2 effect size measures for DTP. One related DTP to mean raw score differences across groups: the other related DTP to the 4/5th rule for adverse impact at successive cut scores. The effects of DTP were examined in the context of personality assessment, professional licensure, and college admissions. Overall, the result indicated that although many items exhibited bias in analyses of the large samples, the net magnitudes of effect on potential selection decisions were nugatory.

College Admission Test↗

PubMed2005

Murine osteoclast formation and function: differential regulation by humoral agents.

Although much has been learned recently of the mechanisms that regulate osteoclastic differentiation, much less is known of the means through which their resorptive activity is controlled. We have developed an assay that allows us to measure resorptive activity while minimizing the confounding effects of the test agent on differentiation. In this assay, murine osteoclasts were harvested from plastic substrates and sedimented onto bone slices in MEM with 10% fetal calf serum. The majority excavate the bone surface within a few hours. We found that the regulation of resorption was distinct from that of osteoclastogenesis. Thus, interferons-beta and -gamma, which strongly suppress, and TGFbeta, which potently stimulates osteoclast differentiation, were without effect on resorption, whereas IL-1alpha, which does not induce osteoclastogenesis, was a strikingly potent stimulus for bone resorption. TNFalpha and IL-1alpha were able to replace receptor activator of nuclear factor-kappaB ligand for stimulation of bone resorption. Protons stimulated bone resorption only in the presence of a resorptive stimulus. PTH, IL-6, and antibodies against osteoclast-associated receptor did not affect bone resorption. Resorption was potently suppressed by 20 mM calcium, 10 microM cyclosporin A, 1 ng/ml calcitonin, and 1 mM dibutyryl cAMP and cGMP. These results show that full functional differentiation of osteoclasts does not require a signal from bone matrix but can occur on plastic and that osteoclastic differentiation and function are regulated by distinct agents.

Animals↗