Biomedical subjects

Y Oiso

Publications and source records attributed to Y Oiso.

At least 127 records · Page 7Linked to original sources

PubMed1993

Vasopressin induces arachidonic acid release through pertussis toxin-sensitive GTP-binding protein in aortic smooth muscle cells: independence from phosphoinositide hydrolysis.

We previously reported that pertussis toxin (PTX) had little effect on arginine vasopressin-induced formation of inositol trisphosphate (IP3) in rat aortic smooth muscle cells [Kondo et al.: Biochemical and Biophysical Research Communications 161:677-682, 1989]. In the present study, we investigated the mechanism of vasopressin-induced arachidonic acid release in rat aortic smooth muscle cells. Vasopressin stimulated both the release of arachidonic acid and the formation of IP3 dose dependently in the range between 10 pM and 1 microM. The effect of vasopressin on arachidonic acid release was more potent than that on the formation of IP3. Quinacrine, a phospholipase A2 inhibitor, significantly suppressed the vasopressin-induced arachidonic acid release but had little effect on the formation of inositol phosphates. NaF, a GTP-binding protein activator, mimicked vasopressin by stimulating the arachidonic acid release. The arachidonic acid release stimulated by a combination of vasopressin and NaF was not additive. PTX partially but significantly suppressed the vasopressin-induced arachidonic acid release. In the cell membranes, PTX catalyzed ADP-ribosylation of a protein with an M(r) of about 40,000. Pretreatment of membranes with 0.1 microM vasopressin in the presence of 2.5 mM MgCl2 and 100 microM GTP markedly attenuated this PTX-catalyzed ADP-ribosylation of the protein in a time-dependent manner. These results strongly suggest that PTX-sensitive GTP-binding protein is involved in the coupling of vasopressin receptor to phospholipase A2 in primary cultured rat aortic smooth muscle cells.

Adenosine Diphosphate Ribose↗

PubMed1993

Effects of retinoic acid on signalling by prostaglandin E2 in osteoblast-like cells.

We investigated the effects of retinoic acid (RA) on the signalling pathways by prostaglandin E2 (PGE2) in osteoblast-like MC3T3-E1 cells. The pretreatment with RA significantly inhibited the formation of inositol phosphates induced by 10 microM PGE2 in a dose-dependent manner in the range between 0.1 nM and 0.1 microM, without affecting protein contents in the cultured cells. This effect of RA was dependent on the time of pretreatment up to 8 h. However, RA had little effect on the formation of inositol phosphates induced by NaF, a GTP-binding protein activator. On the other hand, RA significantly inhibited PGE2-induced cAMP accumulation in a dose-dependent manner between 0.1 nM and 0.1 microM. This effect of RA was dependent on the time of pretreatment up to 8 h. RA also inhibited the cAMP accumulation induced by NaF or forskolin which directly activates adenylate cyclase. These results strongly suggest that RA modulates the signalling by PGE2 in osteoblast-like cells as follows: the inhibitory effect on the phosphoinositide hydrolysis is exerted at the point between PGE2 receptor and GTP-binding protein, and the inhibitory effect on the cAMP production is exerted at a point downstream from adenylate cyclase.

3T3 Cells↗

PubMed1993

Modulation of prostaglandin E2-induced Ca2+ influx by steroid hormones in osteoblast-like cells.

In osteoblast-like MC3T3-E1 cells, we previously reported that prostaglandin E2 (PGE2), a potent bone resorbing agent, stimulates Ca2+ influx (H. Tokuda, M. Miwa, Y. Oiso and O. Kozawa, Cell Signal 1992; 4: 261-266). In this study, we examined the effects of various hormones belonging to the steroid hormone superfamily on PGE2-induced Ca2+ influx in MC3T-E1 cells. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], an active form of vitamin D3, dexamethasone and retinoic acid significantly inhibited the PGE2-induced Ca2+ influx in a dose-dependent manner in these cells. The effects of these hormones were dependent on the time of pretreatment and submaximum inhibitions were observed at 6 h. In contrast, 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3], an inactive form of vitamin D3, 17 beta-estradiol, progesterone, testosterone and triiodothyronine had little effect on the PGE2-induced Ca2+ influx in these cells. These results suggest that, in the steroid hormone superfamily, 1,25-dihydroxyvitamin D3, glucocorticoid and retinoic acid modulate bone metabolism through the inhibition of Ca2+ influx induced by PGE2 in osteoblast-like cells.

Biological Transport↗

PubMed1993

Effects of glucocorticoid on signalling by prostaglandin E2 in osteoblast-like cells.

It is well-known that osteoporosis is a common complication of patients with glucocorticoid excess. We previously reported that dexamethasone inhibits Ca2+ influx induced by prostaglandin E2 (PGE2), a potent bone resorbing agent, in osteoblast-like MC3T3-E1 cells (O. Kozawa, H. Tokuda, J. Kotoyori, A. Suzuki, Y. Ito and Y. Oiso, Prostagland Leuk Essent Fatty Acids, in press). In the present study, we examined the effects of dexamethasone on cyclic adenosine monophosphate (cAMP) accumulation and phosphoinositide hydrolysis by PGE2 in MC3T3-E1 cells. The pretreatment with dexamethasone significantly inhibited cAMP accumulation stimulated by PGE2 in a dose-dependent manner in the range between 10 pM and 1 nM in MC3T3-E1 cells. This effect of dexamethasone was dependent on the time of pretreatment up to 8 h. Dexamethasone also inhibited the cAMP accumulation induced by NaF, an activator of guanosine triphosphate (GTP)-binding protein, or forskolin which directly activates adenylate cyclase. In contrast, dexamethasone had little effect on the formation of inositol phosphates stimulated by PGE2 in MC3T3-E1 cells. These results strongly suggest that glucocorticoid modulates the signal transduction by PGE2 in osteoblast-like cells and that it inhibits PGE2-induced cAMP production without affecting PGE2-induced phosphoinositide hydrolysis.

1-Methyl-3-isobutylxanthine↗

PubMed1993

Galanin as a physiological neurotransmitter in hemodynamic control of arginine vasopressin release in rats.

Previous neuroanatomical studies have revealed a localization of galanin in several nuclei in the brain stem which are involved in the hemodynamic control of arginine vasopressin (AVP) release. The present study, therefore, investigates the contribution of endogenous galanin to the plasma volume-mediated control of AVP release in conscious rats. Injection of synthetic rat galanin (12.5-50 pmol/rat) into the cisterna magna (i.c.s.) suppressed plasma AVP increased by polyethylene glycol-induced hypovolemia (2.45 +/- 0.24 pg/ml at 50 pmol/rat vs. the vehicle group 5.72 +/- 0.69 pg/ml, p < 0.01). In contrast, when plasma AVP was suppressed by isotonic plasma volume expansion, immunoneutralization of endogenous galanin by antigalanin-antibody i.c.s. significantly reversed the suppression (1.02 +/- 0.07 pg/ml vs. vehicle group 0.63 +/- 0.05 pg/ml, p < 0.01) without altering the mean arterial blood pressure. These results suggest that endogenous galanin is physiologically involved in the plasma volume-mediated control of AVP release through an inhibitory action on this pathway.

Animals↗

PubMed1993

Pituitary adenylate cyclase-activating polypeptide stimulates arginine vasopressin release in conscious rats.

The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular (i.c.v.) administration of PACAP raised the plasma AVP concentration in a dose-dependent manner (50-500 pmol/rat), and the maximum effect was obtained at 5 min after the administration. This AVP-releasing effect was not due to a fall of blood pressure, increase of plasma Na or decrease of plasma volume, all of which are known to stimulate AVP release. PACAP had little effect on blood pressure at a low dose, but at higher doses increased it. Vasoactive intestinal peptide (VIP), which is homologous to PACAP, also raised the plasma AVP concentration by i.c.v. injection. An antagonist for VIP receptor, [Lys, Pro, Arg, Tyr]-VIP inhibited the VIP-induced increase of plasma AVP, but had little effect on PACAP-induced increase of plasma AVP. These results suggest that PACAP stimulates AVP release, via specific receptors which are distinct from VIP receptors.

Animals↗

PubMed1993

Possible involvement of inefficient cleavage of preprovasopressin by signal peptidase as a cause for familial central diabetes insipidus.

A transition of G to A at nucleotide position 279 in exon 1 of the vasopressin gene has been identified in patients with familial central diabetes insipidus. The mutation predicts an amino acid substitution of Thr (ACG) for Ala (GCG) at the COOH terminus of the signal peptide in preprovasopression (preproVP). Translation in vitro of wild-type and mutant mRNAs produced 19-kD preproVPs. When translated in the presence of canine pancreatic rough microsomes, wild-type preproVP was converted to a 21-kD protein, whereas the mutant mRNA produced proteins of 21 kD and 23 kD. NH2-terminal amino acid sequence analysis revealed that the 21-kD proteins from the wild-type and the mutants were proVPs generated by the proteolytic cleavage of the 19-residue signal peptide and the addition of carbohydrate. Accordingly, mutant preproVP was cleaved at the correct site after Thr-19, but the efficiency of cleavage by signal peptidase was < 25% that observed for the wild-type preproVP, resulting in the formation of a predominant glycosylated but uncleaved 23-kD product. These data suggest that inefficient processing of preproVP produced by the mutant allele is possibly involved in the pathogenesis of diabetes insipidus in the affected individuals.

Amino Acid Sequence↗

PubMed1993

Glu-47, which forms a salt bridge between neurophysin-II and arginine vasopressin, is deleted in patients with familial central diabetes insipidus.

The arginine vasopressin (AVP) gene was sequenced in a pedigree with familial central diabetes insipidus (DI). When polymerase chain reaction-amplified DNAs from affected subjects were subjected to polyacrylamide gel electrophoresis, fragments including exon 2 displayed two additional, slower migrating bands. These extra bands represented DNA heteroduplexes, indicating that there was a deletion or insertion mutation in exon 2. As the region with such a mutation was identified by direct sequence analysis, polymerase chain reaction-amplified fragments including the region were subcloned and sequenced. A 3-basepair deletion (AGG) out of two consecutive AGG sequences (nucleotides 1824-1829) was identified in one of two alleles. The cosegregation of the mutation with the DI phenotype in the family was confirmed by restriction enzyme analyses. This mutation should yield an abnormal AVP precursor lacking Glu47 in its neurophysin-II (NP) moiety. Since Glu47 is essential for NP molecules to form a salt bridge with AVP, it is very likely that the function of NP as a carrier protein for AVP would be impaired. We suggest that AVP would undergo accelerated proteolytic degradation, and this mechanism would be involved in the pathogenesis of DI in this pedigree.

Adult↗

PubMed1993

Sequence of a variant thyroxine-binding globulin (TBG) in a family with partial TBG deficiency in Japanese (TBG-PDJ).

Thyroxine-binding globulin (TBG) is the major transport protein of thyroid hormones in human serum. In this communication, we present a sequence abnormality of the TBG-gene in a Japanese family manifesting partial TBG deficiency (TBG-PDJ). The propositus was a male with a reduced concentration of TBG (3.2 micrograms/ml). Thyroid function tests suggested that the inheritance of this TBG abnormality was X-linked. The TBG exhibited increased heat-lability compared with the common type TBG (TBG-C). The isoelectric focusing pattern of this TBG molecule was indistinguishable from TBG-C. Genomic DNAs from white blood cells of four members of a TBG-PDJ family were subjected to polymerase chain reaction (PCR), and the products were sequenced. The sequencing of the entire coding exons and exon/intron junctions of TBG allele of the propositus revealed a single nucleotide substitution: CCT (proline) to CTT (leucine) at amino acid 363 of the TBG-C. The heterozygosity as revealed by the direct sequencing of the PCR product correlated with the TBG concentration in serum. The proline to leucine substitution may cause a change in the TBG tertiary structure and result in decreased heat stability, resulting in decreased TBG levels in the affected subjects.

Base Sequence↗

PubMed1993

Gene screening of 23 Japanese families with complete thyroxine-binding globulin deficiency: identification of a nucleotide deletion at codon 352 as a common cause.

Thyroxine-binding globulin (TBG) is a major thyroid hormone transport protein in human serum. Its complete deficiency (TBG-CD) is one of inherited TBG abnormalities that transmit on X-chromosome. We previously reported a nucleotide deletion at codon 352 of the TBG gene (TBG-CDJ) in Japanese families with TBG-CD. To determine the prevalence of this mutation in Japanese with TBG-CD, 23 affected subjects (19 males and 4 females) belonging to unrelated families living in 4 major islands of Japan were analyzed with regard to the mutation at codon 352. Their genomic DNAs were amplified by the polymerase chain reaction with allele specific primers. Nineteen male and four female subjects were shown to have the mutation as hemizygotes and heterozygotes, respectively. It is concluded that TBG-CDJ may be a common cause of TBG-CD in Japanese and might have appeared in the ancestors of the Japanese after the human race divergence.

Alleles↗

PubMed1993

Prostaglandin E2 is a potential mediator of extracellular ATP action in osteoblast-like cells.

Extracellular ATP dose dependently stimulated 45Ca2+ influx even in the presence of nifedipine, a Ca2+ antagonist that inhibits voltage-dependent Ca2+ channel, in osteoblast-like MC3T3-E1 cells. ATP stimulated arachidonic acid release and the synthesis of prostaglandin E2 (PGE2). However, the ATP-induced arachidonic acid release was significantly reduced by chelating extracellular Ca2+ with EGTA. On the other hand, ATP induced DNA synthesis of these cells in a dose-dependent manner in the range between 1 microM and 1 mM. The pretreatment with indomethacin, a cyclooxygenase inhibitor, suppressed both ATP-induced PGE2 synthesis and DNA synthesis in these cells. The inhibitory effect by 50 microM indomethacin on the DNA synthesis was reversed by adding 10 microM PGE2. These results strongly suggest that extracellular ATP stimulates Ca2+ influx resulting in the release of arachidonic acid in osteoblast-like cells and that extracellular ATP-induced proliferative effect is mediated, at least in part, by ATP-stimulated PGE2 synthesis.

Adenosine Triphosphate↗

PubMed1992

Protein kinase C activation amplifies prostaglandin F2 alpha-induced prostaglandin E2 synthesis in osteoblast-like cells.

In cloned osteoblast-like cells, MC3T3-E1, prostaglandin F2 alpha (PGF2 alpha) stimulated arachidonic acid (AA) release in a dose-dependent manner in the range between 1 nM and 10 microM. 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC) activator, which by itself had little effect on AA release, markedly amplified the release of AA stimulated by PGF2 alpha in a dose-dependent manner. 4 alpha-phorbol 12,13-didecanoate, a phorbol ester which is inactive for PKC, showed little effect on the PGF2 alpha-induced AA release. 1-oleoyl-2-acetylglycerol (OAG), a specific activator for PKC, mimicked TPA by enhancement of the AA release induced by PGF2 alpha. H-7, a PKC inhibitor, markedly suppressed the effect of OAG on PGF2 alpha-induced AA release. Quinacrine, a phospholipase A2 inhibitor, showed partial inhibitory effect on PGF2 alpha-induced AA release, while it suppressed the amplification by OAG of PGF2 alpha-induced AA release almost to the control level. Furthermore, TPA enhanced the AA release induced by melittin, known as a phospholipase A2 activator. On the other hand, TPA inhibited the formation of inositol trisphosphate stimulated by PGF2 alpha. Under the same condition, PGF2 alpha indeed stimulated prostaglandin E2 (PGE2) synthesis and TPA markedly amplified the PGF2 alpha-induced PGE2 synthesis as well as AA release. These results indicate that the activation of PKC amplifies PGF2 alpha-induced both AA release and PGE2 synthesis through the potentiation of phospholipase A2 activity in osteoblast-like cells.

Animals↗

PubMed1992

Cross-talk regulation between cyclic AMP production and phosphoinositide hydrolysis induced by prostaglandin E2 in osteoblast-like cells.

In cloned osteoblast-like MC3T3-E1 cells, PGE2 stimulated both cAMP accumulation and the formation of inositol trisphosphate (IP3) dose dependently. The cAMP accumulation showed the peak value at 5 min and decreased thereafter, whereas the IP3 formation reached a plateau almost within 10 min and sustained it up to 30 min. The effect of PGE2 on cAMP accumulation (EC50 was 80 nM) was more potent than that on IP3 formation (EC50 was 0.8 microM). 12-O-Tetradecanoyl-phorbol-13-acetate (TPA), a protein kinase C (PKC)-activating phorbol ester, reduced the PGE2-induced cAMP accumulation, whereas 4 alpha-phorbol 12,13-didecanoate, a PKC-nonactivating phorbol ester, had little effect on the cAMP accumulation. 1-Oleoyl-2-acetyl-glycerol, a specific activator for PKC, inhibited PGE2-induced cAMP accumulation. TPA had little effect on cAMP accumulation induced by forskolin or NaF, a GTP-binding protein activator. So, the effect of TPA is presumed to be exerted at the point between the PGE2 receptor and Gs. On the other hand, forskolin and dibutyryl cAMP had little effect on the IP3 formation stimulated by PGE2. H-7, a PKC inhibitor, enhanced the PGE2-induced cAMP accumulation in comparison with HA1004, a control for H-7. Our data suggest that PGE2 regulates cAMP production through self-induced activation of PKC. These results strongly suggest that there is an autoregulatory mechanism in PGE2 signaling, and PGE2 modulates osteoblast functions through a cross-talk interaction between cAMP production and phosphoinositide hydrolysis in osteoblast-like cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1992

Inhibitory effect of 17 beta -estradiol on prostaglandin E2-induced phosphoinositide hydrolysis in osteoblast-like cells.

We examined the effect of estradiol on PGE2-induced phosphoinositide hydrolysis and cAMP production in cloned osteoblast-like MC3T3-E1 cells. 17 beta -Estradiol pretreatment significantly inhibited the formation of inositol phosphates induced by 10 microM PGE2 in a dose-dependent manner between 1 pM and 10 nM. This effect of 17 beta -estradiol was dependent on the time of pretreatment and submaximum inhibition was observed at 4 h. However, 17 beta -estradiol had little effect on the formation of inositol phosphates induced by 20 mM NaF, a GTP-binding protein activator. The cAMP production induced by PGE2 was not influenced by 17 beta -estradiol. These results suggest that 17 beta -estradiol modulates the signal transduction by PGE2 and that the effect seems to be exerted between PGE2 receptor and the GTP-binding protein coupled to phospholipase C in osteoblast-like MC3T3-E1 cells.

Animals↗

PubMed1992

Activation of protein kinase C inhibits 45Ca-accumulation in cultures of osteoblast-like cells: possible involvement of insulin-like growth factor-I.

In a previous report, we have demonstrated that exogenous insulin-like growth factor-I (IGF-I) stimulates 45Ca-accumulation into extracellular matrix in long-term cultures of osteoblast-like MC3T3-E1 cells and that 45Ca-accumulation occurs even in the cultures without exogenous IGF-I. In this study, effects of protein kinase C (PKC) on IGF-I secretion and 45Ca-accumulation into extracellular matrix were examined in 6-week cultured MC3T3-E1 cells. The MC3T3-E1 cells secreted IGF-I spontaneously. The PKC activator, 12-O-tetradecanoylphorbol-13-acetate (TPA) suppressed IGF-I secretion in a dose-dependent manner. 4 alpha-Phorbol 12,13-didecanoate (4 alpha-PDD), which is inactive for PKC, had little effect on the secretion. 1-Oleoyl-2-acetylglycerol, a specific activator for PKC, also suppressed the IGF-I secretion dose dependently. H-7, a PKC inhibitor, recovered the inhibitory effect of TPA. On the other hand, TPA inhibited the 45Ca-accumulation into extracellular matrix in cultures of these cells dose dependently, whereas 4 alpha-PDD was ineffective in this capacity. The TPA-induced inhibition of 45Ca-accumulation was recovered almost to the control level by H-7. Exogenous IGF-I recovered the inhibitory effect of TPA on 45Ca-accumulation. In spite of the inhibitory effects of TPA as above, TPA had little effect on DNA synthesis in these cells. These results suggest that the activation of PKC inhibits calcification via suppression of IGF-I secretion in osteoblast-like cells.

Animals↗

PubMed1992

Autoregulation of prostaglandin E2-induced Ca2+ influx in osteoblast-like cells: inhibition by self-induced activation of protein kinase C.

In cloned osteoblast-like MC3T3-E1 cells, prostaglandin E2 (PGE2) stimulated 45Ca2+ influx even in the presence of nifedipine, a Ca2+ antagonist that inhibits voltage-dependent Ca2+ channel, in a dose-dependent manner, attaining a maximum at 0.5 microM. Dose of PGE2 above 0.5 microM caused less than maximal stimulation. While PGE2 stimulated the formation of inositol trisphosphate dose dependently in the range between 1 nM and 10 microM. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC)-activating phorbol ester, which by itself had little effect on 45Ca2+ influx, significantly suppressed the 45Ca2+ influx induced by PGE2 in a dose-dependent manner between 1 nM and 1 microM. 4 alpha-Phorbol 12,13-didecanoate, a phorbol ester which is inactive for PKC, showed little effect in this capacity. Staurosporine, a PKC inhibitor, enhanced the PGE2-induced 45Ca2+ influx. On the other hand, dibutyryl cAMP had little effect on the 45Ca2+ influx induced by PGE2. Our data suggest that PGE2 regulates Ca2+ influx through self-induced activation of PKC. These results indicate that there is an autoregulatory mechanism in signal transduction by PGE2, and PGE2 modulates osteoblast functions through the interaction between Ca2+ influx and phosphoinositide hydrolysis in osteoblast-like cells.

Animals↗

PubMed1992

Mechanism of prostaglandin E2-induced arachidonic acid release in osteoblast-like cells: independence from phosphoinositide hydrolysis.

We previously reported that pertussis toxin (PTX)-sensitive GTP-binding protein is involved in the coupling of prostaglandin E2 (PGE2) receptor to phospholipase C in osteoblast-like MC3T3-E1 cells (1). In the present study, we analyzed the mechanism of PGE2-induced arachidonic acid (AA) release in MC3T3-E1 cells. PGE2 stimulated the release of AA and the formation of inositol trisphosphate (IP3) dose dependently in the range between 1 nM and 10 microM. The effect of PGE2 on AA release (ED50 was 80 nM) was more potent than that on IP3 formation (ED50 was 0.8 microM). Quinacrine, a phospholipase A2 inhibitor, suppressed the PGE2-induced AA release but had little effect on the IP3 formation. NaF, a GTP-binding protein activator, mimicked PGE2 by stimulating the AA release. The AA release stimulated by a combination of PGE2 and NaF was not additive. PTX had little effect on the PGE2-induced AA release. These results strongly suggest that the AA release and the phosphoinositide hydrolysis are separately stimulated by PGE2 in osteoblast-like cells, and the PGE2-induced AA release is mediated by PTX-insensitive GTP-binding protein.

Arachidonic Acid↗

PubMed1992

Proliferative effect of PGD2 on osteoblast-like cells; independent activation of pertussis toxin-sensitive GTP-binding protein from PGE2 or PGF2 alpha.

PGD2 stimulated DNA synthesis and decreased alkaline phosphatase activity dose-dependently between 10 nM and 10 microM in osteoblast-like MC3T3-E1 cells. PGD2 had little effect on cAMP production, but caused very rapid enhancement of phosphoinositide (PI) hydrolysis dose-dependently between 10 nM and 10 microM. The formation of inositol trisphosphate (IP3) induced by PGD2 reached the peak within 1 min and decreased thereafter, which is more rapid than that induced by PGE2 or PGF2 alpha and both PGE2 and PGF2 alpha affected PGD2-induced IP3 formation additively. Pertussis toxin (PTX) inhibited both PGD2-induced formation of inositol phosphates and DNA synthesis. The degree of these PTX (1 micrograms/ml)-induced inhibitions was similar. In addition, neomycin, a phospholipase C inhibitor, inhibited PGD2-induced DNA synthesis as well as the formation of IP3, and the patterns of both inhibitions were similar. In the cell membranes, PTX-catalyzed ADP-ribosylation of a 40-kDa protein was significantly attenuated by pretreatment of PGD2. Time course of the attenuation of PTX-catalyzed ADP-ribosylation by PGD2 was apparently different from that by PGE2 or PGF2 alpha. These results indicate that PGD2 activates PTX-sensitive GTP-binding protein independently from PGE2 or PGF2 alpha and stimulates PI hydrolysis resulting in proliferation of osteoblast-like cells.

Adenosine Diphosphate Ribose↗