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Biomedical subjects

V Shen

Publications and source records attributed to V Shen.

At least 55 records · Page 3Linked to original sources
PubMed1995

Short-term changes in histomorphometric and biochemical turnover markers and bone mineral density in estrogen-and/or dietary calcium-deficient rats.

Both estrogen and dietary calcium deficiencies are important risk factors in the pathogenesis of osteoporosis. We used an animal model of postmenopausal osteoporosis to study histomorphometric and bone turnover markers and bone mineral changes induced by short-term (1 month) estrogen and/or dietary calcium deficiency in the mature rat. Seven groups of rats were studied: 1) basal; 2) sham, fed a calcium-deficient diet (0.1% Ca, Sham-LoCa); 3) sham, fed a regular-calcium diet (1.0% Ca, Sham-RCa); 4) ovariectomy (ovx), on a calcium-deficient diet (Ovx-LoCa); 5) ovx, on a regular-calcium diet (Ovx-RCa); 6) ovx, on a calcium-deficient diet with estrogen replacement (Ovx-LoCa-Est); and 7) ovx, on a regular-calcium diet with estrogen replacement (Ovx-RCa-Est). When compared with sham-operated animals on a regular calcium diet (Sham-RCa), either deficiency alone elevated the turnover markers osteocalcin (BGP) (Sham-LoCa 24.5%; Ovx-RCa 54.7%) and pyridinoline (Sham-LoCa 48.3%, Ovx-RCa 112.3%). Reductions in cancellous bone mass (Cn-BV/TV, Sham-LoCa -26.5%, Ovx-RCa -41.1%) and trabecular connectivity (Node.Node, Sham-LoCa -54.5%, Ovx-RCa -62.6%) were observed. Combined deficiencies (Ovx-LoCa) showed a greater change (BGP, +66.0%; pyridinoline +117.7%; Cn-BV/TV -64.4%; Nd.Nd -95.6%). Estrogen treatment was effective in preventing bone loss from both estrogen and calcium deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1995

Temporal changes in cancellous bone structure of rats immediately after ovariectomy.

To understand the structural changes accompanying estrogen deficiency-induced bone loss, we examined the temporal changes in cancellous bone structure in an animal model of postmenopausal osteoporosis. Matured rats were subjected to bilateral ovariectomy, and groups of eight animals were sacrificed at 5-day intervals. Histomorphometric and trabecular strut analyses of the excised proximal tibia, and bone mineral density measurement of the distal femur, were used to investigate cancellous bone loss as a result of estrogen deficiency. There was an immediate increase in bone turnover after ovariectomy, as evidenced by rapid increases in osteoclast surface (400%) and bone formation rate (270%). The resultant time-dependent decrease in cancellous bone volume was highly related to a decrease in trabecular plate number and connectivity parameters, but was not related to the thickness of the remaining cancellous plates. Our results suggest that cancellous bone loss due to estrogen deficiency is the result of decreased connectivity, likely due to osteoclast perforation of trabecular plates, followed by complete removal of the plate without prior generalized thinning.

Animals↗
PubMed1994

High-dose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skeleton.

The effects of acute pharmacologic steroid treatment on skeletal and mineral metabolism were assessed in 56 multiple sclerosis patients who were to receive 1 g intravenous methylprednisolone for 10 days, followed by a 4 day intravenous and 28 day oral glucocorticoid taper. Serum and urine samples were obtained at baseline and then within 3 days, 1, 2, and 3 weeks after beginning steroids. A subset of patients (n = 11) had sampling throughout the 6 weeks of steroid administration and up to 8 weeks afterward. All mean basal biochemistries were normal except 25(OH)D, which was in the "insufficient" range (25-50 nM) at 10 nM. During and after steroid administration, there were no changes in ionized calcium, 25(OH)D, urinary hydroxyproline, or pyridinoline. There was an increase in 1,25(OH)2D and a decrease in serum phosphorus, accompanied by an increase in urinary phosphate clearance, within 3 days of administration (p < 0.006). Serum osteocalcin (BGP) decreased to below assay sensitivity limits within 3 days of steroid administration (p < 0.0002), increasing thereafter but remaining at 50% of baseline by the third week. PTH(1-84) increased to a peak at week 2 (p < 0.02), after both the 1,25(OH)2D peak and the serum phosphorus nadir. Tartrate-resistant acid phosphatase, urinary calcium, and urinary cyclic AMP all increased above baseline (p < 0.05) with a pattern similar to that of PTH. To investigate further the immediate effects of steroid administration, serum samples were obtained at the same four times on both the day before and the day after the first intravenous methylprednisolone dose in a randomly chosen subset of patients (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Effects of estrogen on response to edetic acid infusion in postmenopausal osteoporotic women.

We and others have hypothesized that estrogen helps preserve bone mass by affecting the PTH/vitamin D regulation of skeletal metabolism. To evaluate this theory, we tested the effect of estrogen administration on parathyroid sensitivity to hypocalcemic challenge. Subjects were postmenopausal osteoporotic women recruited from a tertiary care clinic (9 untreated and 12 receiving hormone replacement therapy at the time of the investigation). After baseline serum and urine testing, edetic acid (50 mg/kg) was infused over a 2-h period. Serum and urine samples were obtained over 5 h and 24 h after beginning the infusion. Serum ionized calcium dropped equally in both groups of women. There were overall group differences in PTH-(1-84) secretion (P < 0.02), with a greater peak (P < 0.04) and a longer period of elevation (P < 0.01) in the untreated than in the hormone-treated osteoporotic women. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] and phosphorus as well as urinary phosphate and cAMP responded similarly in the two groups of women. Estrogenized osteoporotic women demonstrate a smaller PTH increment to hypocalcemia, indicating that the parathyroid has reduced sensitivity under the influence of estrogen. Despite the smaller PTH increase in estrogenized individuals, renal responses to PTH were the same as those in untreated osteoporotic women, implying an estrogen-mediated increase in the sensitivity of the kidney to PTH.

Administration, Oral↗
PubMed1994

High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis.

BACKGROUND: Female patients with multiple sclerosis (MS) are at risk for osteoporosis because of gender, immobility, and corticosteroid use. METHODS: Bone mineral density (BMD) was measured by dual x-ray absorptiometry in 80 female MS patients admitted to a tertiary care hospital. All patients completed a questionnaire that included measurements of dietary intake and sunlight exposure. Biochemical indices of bone metabolism and turnover were measured in a random sample of 52 patients. RESULTS: BMD of the lumbar spine and femoral neck was 1 to 2 SDs lower in MS women compared with a healthy reference population. BMD was lower in patients with more severe MS. The mean 25(OH)D level of the sample population (43 nmol/l) was in the insufficient range, and 12 patients (23%) had frank vitamin D deficiency (< 25 nmol/l). BMD and age-related BMD (z scores) at all skeletal sites measured were lowest when 25(OH)D levels were deficient. Parathyroid hormone (PTH) was frankly elevated in 13% of patients. PTH levels were negatively correlated with 25(OH)D levels and with BMD. Dietary intake of vitamin D was below the recommended level in 80% of patients, and 40% reported no weekly sunlight exposure. After controlling for age, cumulative steroid use was not a determinant of BMD. CONCLUSIONS: BMD was significantly reduced in female MS patients, which might increase fracture risk two- to threefold. Vitamin D deficiency with secondary hyperparathyroidism is prevalent and is probably a significant cause of low BMD in this population. Vitamin D deficiency in the female MS patient might be safely and inexpensively corrected by the routine use of vitamin D supplements.

Adult↗
PubMed1993

Estrogen protection against bone resorbing effects of parathyroid hormone infusion. Assessment by use of biochemical markers.

OBJECTIVE: Because parathyroid hormone (PTH) stimulates bone resorption, resistance to its actions might help maintain bone mass. We tested the hypothesis that the effects of estrogen on bone are accomplished in part by decreasing the sensitivity of the skeleton to the resorbing effects of PTH. STUDY DESIGN: Comparison of response to PTH infusion in untreated and estrogen-treated postmenopausal women with osteoporosis. INTERVENTION: (1-34) human PTH, 0.55 U/(kg.h), was infused intravenously over 20 hours. SETTING: The inpatient clinical research unit of a referral hospital. PATIENTS: Women with primary postmenopausal osteoporosis who were untreated (n = 15) or treated with estrogen (n = 17). MAIN OUTCOME MEASURES: Skeletal turnover indices including hydroxyproline, deoxypyridinoline, pyridinoline, tartrate-resistant acid phosphatase, alkaline phosphatase, bone Gla protein, and insulin-like growth factor-1. RESULTS: All basal indices were higher in untreated than in estrogen-treated women, but statistical differences were seen only for deoxypyridinoline and pyridinoline. During the 20-hour infusion, hydroxyproline/creatinine increased 0.023 mumol/mumol in untreated women but only 0.010 mumol/mumol in estrogen-treated women (P < 0.05). Corresponding changes for deoxypyridinoline/creatinine were 14.6 mumol/mumol and 3.5 mumol/mumol (P = 0.06). Tartrate-resistant acid phosphatase and pyridinoline increased only in untreated group. A circadian rhythm in circulating bone Gla protein was seen in both groups without clear PTH-induced effects or differences between groups. Alkaline phosphatase levels decreased and insulin-like growth factor-1 levels increased in both groups with no distinction between untreated and estrogen-treated women [corrected]. CONCLUSION: The estrogenized postmenopausal osteoporotic skeleton is less sensitive to the bone resorbing effects of acutely administered PTH. There are no differential effects on bone formation.

Aged↗
PubMed1993

Urinary hydroxypyridinium crosslinks of collagen as markers of bone resorption and estrogen efficacy in postmenopausal osteoporosis.

Estrogen deficiency-induced bone loss has been associated with accelerated bone turnover. Levels of some biochemical markers, such as serum osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), and urinary hydroxyproline (OHP), have been shown to be related to the rate of bone turnover. They may therefore be useful in identifying the individual at risk for osteoporosis and monitoring the efficacy of the treatment. Two recently discovered markers, urinary pyridinoline (PYD) and deoxypyridinoline (DPD), are apparently directly related to bone matrix degradation and may be more accurate markers of bone resorption than OHP or TRAP. To evaluate the effects of menopause, osteoporosis, and estrogen replacement on the excretion of these new markers, we measured the levels of PYD and DPD and other biochemical markers of bone turnover in four groups of women, premenopausal healthy (PRE), postmenopausal healthy (POST), postmenopausal osteoporotic (UTO), and postmenopausal osteoporotic with estrogen treatment (ETO). Significant increases in PYD, DPD, BGP, TRAP, and OHP were found in POST and UTO groups compared with PRE. These increases were blunted by estrogen treatment when the levels of each of the markers returned to PRE levels. When comparing POST and UTO groups, significant increases were observed in UTO only for PYD, DPD, and urinary calcium but not for OHP, BGP, or TRAP. With subgroups matched for age and years from menopause, only DPD discriminated between POST and UTO. Indices of bone formation covaried with markers of bone resorption in the total population.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1993

Calcium homeostasis of an elderly population upon admission to a nursing home.

OBJECTIVE: To evaluate the skeletal health, calcium, and vitamin D homeostasis of patients upon their entry to a long-term-care facility. Factors that could contribute to the risk of future osteoporotic fractures were also evaluated. DESIGN: Cross-sectional study. PATIENTS: Two hundred eighty-seven consecutive admissions were invited to participate; 109 patients were recruited into the study. MEASUREMENTS: A high prevalence of low to low-normal circulating levels of 25(OH)D was found in nursing home residents upon their admission to the nursing home, with 86% of the patients having circulating 25(OH)D levels of less than 50 nmol/L and 41% having levels below 25 nmol/L. Frankly elevated parathyroid hormone levels were found in 16% of the patients. Additionally, alkaline phosphatase and osteocalcin levels were elevated in 23% and 13% of the patients, respectively. Bone mineral measurements were in the osteoporotic range for 85% of the nursing home residents. Bone density results for females with a history of any classic osteoporotic fracture were significantly lower than for those with no fracture history (68.5 arbitrary units (AU) for those with no fracture history, 58.8 AU in those with history of hip fracture; P < 0.05). The bone mineral measurements were higher in women with adequate 25(OH)D compared with women with deficient or borderline 25(OH)D with and without fracture history. Levels of 25(OH)D were positively correlated with urine calcium/creatinine (r = .24; P = 0.03) and 1,25(OH)2D (r = .28; P = 0.01) and were negatively correlated with 1-84 PTH (r = -.24; P = 0.02). CONCLUSION: Hypovitaminosis D is prevalent among elderly patients entering a nursing home with secondary hyperparathyroidism and apparently increased bone turnover present in patients with circulating 25(OH)D levels below 50 nmol/L. Bone density measurements showed that a majority of the individuals entering a nursing home are osteoporotic. There is a positive association between 25(OH)D levels and bone mass and a negative association between 25(OH)D levels and a history of fracture.

Activities of Daily Living↗
PubMed1993

Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol.

To evaluate the potential use of a combination of antiresorption and bone formation-promoting agents as a treatment for postmenopausal osteoporosis, we examined the effects of combined and separate administration of estrogen (17 beta-estradiol, 30 micrograms/kg per d, s.c.) and parathyroid hormone (rPTH [1-34], 40 micrograms/kg per d, s.c.) on the proximal tibia of ovariectomized (Ovx) rats. The treatments lasted for 4 wk and were initiated 1, 3, and 5 wk after surgery. Ovx resulted in rapid loss of cancellous bone volume (Cn-BV/TV) as well as trabecular connectivity, as determined by two dimensional strut analysis. When administered in a preventive mode, treatment beginning 1 wk post-Ovx, estrogen or PTH treatment alone preserved Cn-BV/TV and trabecular connectivity, and combined estrogen and PTH treatment caused a 40% increment in Cn-BV/TV while maintaining comparable trabecular connectivity with that seen in the Sham-operated animals. When administered in a curative mode to rats with established osteoporosis, treatments beginning 3 or 5 wk post-Ovx, estrogen or PTH treatment alone prevented further loss of connectivity and Cn-BV/TV, whereas the combined treatment resulted in as much as a 300% improvement in one of the parameters of trabecular connectivity, node to node strut length, and a 106% increase in Cn-BV/TV, with respect to the bone status at the initiation of treatment. The beneficial effects of this combined treatment derive from estrogen's ability to prevent accelerated bone resorption and, simultaneously, PTH's promotion of bone formation. These data demonstrate, in an animal model, that therapies can be devised to cure the skeletal defects associated with established osteoporosis.

Animals↗
PubMed1993

Subcutaneous administration of the amino-terminal fragment of human parathyroid hormone-(1-34): kinetics and biochemical response in estrogenized osteoporotic patients.

A standard dose (400 U or 25 micrograms) of human (h) PTH-(1-34) was administered sc in 11 estrogen-treated patients with postmenopausal osteoporosis. Increments in circulating hPTH-(1-34) were brisk, peaking at 30 min, with variable peak levels averaging 10 times normal. Clearance of the peptide from the circulation followed an expontential pattern, with a mean t1/2 of 75 min. Peptide administration was followed by an immediate decline in serum concentrations of PTH-(1-84), which remained suppressed at about 65% of the basal value for the duration of the study (4 h). Serum calcium did not increase until 120 min, thus occurring after the diminution in PTH-(1-84). Serum phosphorus declined promptly as urinary phosphate excretion increased. There were no clear changes in urinary calcium excretion, but urinary cAMP excretion increased within 120 min. In 9 of 11 patients, the serum concentration of 1,25-dihydroxyvitamin D increased, with mean levels increasing progressively after 90 min to approximately 30% above baseline (P < 0.05). In conclusion, sc administration of 25 micrograms hPTH-(1-34) produces significant short term changes in mineral homeostasis that appear to be mediated by the kidney, parathyroid gland, and skeleton, with the latter displaying the most delayed response.

Calcitriol↗
PubMed1993

Multiple spinal meningiomas: a case of 47 distinct lesions in the absence of neurofibromatosis or identified chromosomal abnormality.

The authors present a unique case of multiple spinal meningiomas with the late development of intracranial lesions. The patient had 47 distinctly separate, yet histologically identical, lesions excised, with many others noted at the time of surgery and by radiographic studies. He was evaluated for neurofibromatosis and was found to have neither Type I nor Type II. Genetic analysis, including restriction fragment length polymorphism analysis, was performed and detected no abnormalities.

Adult↗
PubMed1993

Decreased endogenous circulating Steel factor (SLF) levels following allogeneic and autologous BMT: lack of an inverse correlation with post-BMT myeloid engraftment.

We have previously demonstrated an inverse relationship between circulating endogenous G-CSF levels and myeloid engraftment post-BMT. A new early-acting hematopoietic growth factor, Steel factor (SLF), has recently been demonstrated to induce the proliferation of early hematopoietic progenitor cells and synergistically stimulate committed progenitor cells in the presence of lineage-specific CSFs. In this pilot study, we determined the temporal relationship between endogenous SLF levels and the circulating absolute neutrophil count (ANC) (myeloid engraftment) in both children and adults undergoing both allogeneic and autologous BMT. Pre-BMT SLF levels were 2600 +/- 100 pg/ml compared to significantly lower levels of G-CSF (30-50 pg/ml). The circulating SLF level was significantly decreased throughout the post-BMT period (ANC < or = 200 x 10(6)/l: 1500 +/- 600 pg/ml; ANC 200-500 x 10(6)/l: 1780 +/- 130 pg/ml; ANC > or = 500 x 10(6)/l: 1690 +/- 110 pg/ml) (p < 0.001). There was a lack of an inverse relationship between the circulating SLF level and the ANC (r = -0.43) (p = NS). For comparison, SLF levels from immune thrombocytopenia (platelet < = or 20 x 10(9)/l) and chemotherapy-induced neutropenia patients (ANC < or = 200 x 10(6)/l) were similar to pre-BMT levels but significantly higher than post-BMT levels (p < or = 0.02 and < or = 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effects of combined and separate intermittent administration of low-dose human parathyroid hormone fragment (1-34) and 17 beta-estradiol on bone histomorphometry in ovariectomized rats with established osteopenia.

To evaluate the potential use of a combination of parathyroid hormone (PTH) and estrogen as therapy for osteoporosis, we examined the effects of combined and separate administration of low-dose PTH and estradiol in ovariectomized rats with established osteopenia. Ovariectomized rats were untreated for 5 weeks after surgery and then injected s.c. with vehicle (Ovx + V), 1-34 hPTH (2.5 micrograms/kg/day) (Ovx + P), 17 beta-estradiol (50 micrograms/kg/day) (Ovx + E), or a combination of these (Ovx + P + E), for a further 4 weeks. We found no differences in serum calcium, tubular reabsorption of phosphate, or 25OHD. 1,25(OH)2D levels were significantly higher in Ovx + P and lower in Ovx + E, when compared with Ovx + V. Though there was no change in bone mineral density (BMD) in the diaphysis region of femurs, reduction of BMD in the distal region of the femurs in Ovx + V was reversed in Ovx + E and Ovx + P + E. Compared with Ovx + V, Ovx + P and Ovx + P + E had significantly higher cancellous bone volume (Cn-BV/TV) whereas Ovx + E showed a nonsignificant increase. When indices of bone turnover were examined, PTH alone showed a small but not significant improvement in bone formation rate (BFR). Increased osteoclast surface (OCS), as the result of ovariectomy, was inhibited in Ovx + E and Ovx + P + E. Estrogen alone (Ovx + E) severely inhibited BFR, but co-administration of PTH and estrogen (Ovx + P + E) showed an impressive reversal of such inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Lack of changes in histomorphometric, bone mass, and biochemical parameters in ovariohysterectomized dogs.

A predictable animal model with skeletal remodeling characteristics similar to those of humans is needed to facilitate the understanding of the mechanism of postmenopausal osteoporosis. We have utilized the ovariohysterectomized (Ovh) dog to examine cellular and biochemical responses to estrogen depletion and PTH stimulation. Histomorphometric measurements of bone biopsies taken prior to (first biopsy) and five months after the operation (second biopsy) showed no significant differences in static and dynamic parameters. Bone mineral density of the excised vertebrae displayed the same values between the two groups six months after surgery. Between the second biopsy and sacrifice, two infusion studies were performed. A two-hour infusion of EDTA followed by a two-hour recovery period elicited a rapid response in PTH production, highly correlated to the changes in ionized calcium, but no significant difference in response was observed between Sham and Ovh groups. A short-term (24-h) infusion of 1-34 hPTH increased circulating ionized calcium and 1,25-(OH)2-D levels to a similar extent in both groups. The levels of alkaline phosphatase were constant and both groups showed a small but nonsignificant increase in osteocalcin. The lack of sizable responses in histomorphometric, bone mass, and biochemical parameters may limit the utility of dogs for the study of cancellous bone loss in ovarian-dysfunction osteoporosis.

Animals↗
PubMed1991

Quantitation of Ca ATPase, feet and mitochondria in superfast muscle fibres from the toadfish, Opsanus tau.

The muscle band surrounding the swimbladder of the toadfish (Opsanus tau) is one of the fastest known muscles in vertebrates. Rapid, non-fused twitches are responsible for the characteristic sound produced by the organ by both male and female toadfish. We have quantitated the membrane systems (transverse (T) tubules, sarcoplasmic reticulum (SR) and mitochondria), and some of their proteins (Ca2+ ATPase, or calcium pump, and foot protein or Ca2+ release channel) in these muscle fibres. As expected from the well-known morphology, the content of Ca2+ release and Ca2+ uptake proteins are considerably higher than in slower twitch fibres (e.g. fast-twitch and slow-twitch fibres in hind legs of mammals). Unexpectedly, the increment in ATPase is much larger than the increment in foot protein. The ATPase to foot ratio in muscle fibres from the swimbladder of males and females is higher by a factor of five to seven than in guinea pig fast-twitch fibres. We conclude that calcium uptake is a limiting factor in the ability to sustain the trains of high frequency, non-fused synchronous contractions of which these fibres are capable. Sexual dimorphism is demonstrated in the content of mitochondria (higher in males) and in the density of junctional feet (higher in females). The former is probably related to the more continuous activity during the males' mating call but the latter is to be demonstrated.

Air Sacs↗
PubMed1991

Effects of cyclosporine A on chick osteoclasts in vitro.

We have studied the effects of cyclosporine A (CsA) on basal and bovine parathyroid hormone (1-34) (bPTH)-stimulated bone resorption by osteoclasts in 24-hour cultures of chick long bone cells. At a high concentration (10 micrograms/ml), CsA had a cytotoxic effect on both osteoclasts and mononuclear cells in the culture. At 1 microgram/ml, CsA inhibited basal and bPTH-stimulated bone resorption but was not cytotoxic over 24 hours. We also studied the binding of bPTH to the osteoblastic cell line, Saos-2, and chick long bone cells in suspension culture. CsA inhibited bPTH binding in Saos-2 in a dose-dependent manner; inhibition of binding was also observed in chick bone cells. The effects of CsA on osteoclast viability and resorptive function may be due to a direct effect on the osteoclasts and/or to an interaction with the nonosteoclastic cell population in the culture.

Analysis of Variance↗
PubMed1991

Regulation of plasminogen activator and plasminogen activator inhibitor production by growth factors and cytokines in rat calvarial cells.

Fetal rat osteoblast-enriched calvarial cells were used to study the effects of various growth factors and cytokines on plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activities and the possible relationship of these effects to bone resorption. Confluent cultures were exposed to various factors under serum-free conditions, and levels of PA and PAI activities were examined in both conditioned medium (CM) and cell layer using the 125I-fibrin plate assay, fibrin zymogram, and reverse fibrin zymogram. According to the 125I-fibrin plate assay or zymogram, incubation of cells with acidic fibroblast growth factor (aFGF), basic FGF (bFGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) elevated the PA activity in the CM as well as in the cell layer extract. Incubation with interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and insulin-like growth factor I (IGF-I) produced no change in PA activity in either CM or cell layer. Addition of transforming growth factor beta (TGF beta) to calvarial cells resulted in nearly undetectable PA activity in CM with the fibrin plate assay but increased PA activity on the fibrin zymogram after PAI was separated from PA by SDS-PAGE. A reverse fibrin zymogram indicated that PAI activity was greatly enhanced in TGF beta-treated CM. TGF beta treatment also increased PA activity in the cell layer of calvarial cells. Treatment of calvarial cells with bFGF and PDGF slightly increased PAI secretion into medium. This increase, however, was not as dramatic as the increase of PA induced by these two agents. IL-1 alpha and TNF alpha did not change PAI concentration in CM. No detectable PAI activity was found in the cell layer in control and treated groups. The PA found in the CM and cell layer of rat calvarial cells was the urokinase type; the PAI stimulated by TGF beta was the endothelial cell type, PAI-1. The regulation of PA activity by growth factors and cytokines did not correlate with their resorption-stimulating activities. Thus, PA secreted by osteoblasts may not be the only factor involved in the initiation of bone resorption. Delineation of the function of PA and PAI in the physiology of bone tissue awaits further studies.

Animals↗