Therapeutic Mechanism of Chinese Medicine on the Healing of Early and Middle Fractures in Rabbits Under the Expression Level of Bone Morphogenetic Protein-2 (BMP-2) in Bone Tissue

2022 ◽  
Vol 12 (1) ◽  
pp. 45-51
Author(s):  
Hegui Xu ◽  
Yang Liu ◽  
Yuxiong Li ◽  
Wenbing Luo ◽  
Zhenyang Liu ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Bone Morphogenetic Protein ◽  
Expression Level ◽  
Bone Morphogenetic Protein 2 ◽  
Bone Collagen ◽  
Control Group ◽  
Type I ◽  
Type Ii ◽  
Morphogenetic Protein ◽  
Therapeutic Mechanism

In order to explore the therapeutic mechanism of Chinese medicine on the healing of rabbits early and middle fractures, a rabbit fracture model was established in this study. The study was divided into several groups, i.e., treatment group (TG) (fed with Chinese medicine Capsule) and control group (CG) (fed with normal saline (NS)). The materials were collected at 1, 3, and 5 weeks after the start of the experiment for analysis. The experiment content included: callus Hematoxylin-Eosin staining (HE staining); Bone Morphogenetic protein-2 (BMP-2) protein level detection; Type I and type II bone collagen (BC) detection; and serum biochemical factors detection. The experimental results showed that the formation of callus in the TG was better than in the CG; the BMP-2 protein expression level in the TG was higher than in the CG, and there were statistically significant differences (SSDs); the type I and type II BC levels in the TG were higher than the CG, there were SSDs; the levels of serum calcium (SC), phosphorus ion (PI), and alkaline phosphatase (ALP) in the TG were also higher than in the CG, and there were SSDs.

scholarly journals Differential Regulation of the Two Principal Runx2/Cbfa1 N-Terminal Isoforms in Response to Bone Morphogenetic Protein-2 during Development of the Osteoblast Phenotype

Endocrinology ◽  
2001 ◽  
Vol 142 (9) ◽  
pp. 4026-4039 ◽  
Author(s):  
Chaitali Banerjee ◽  
Amjad Javed ◽  
Je-Yong Choi ◽  
Jack Green ◽  
Vicki Rosen ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Osteoblast Differentiation ◽  
Mesenchymal Cell ◽  
Cellular Protein ◽  
C2c12 Cells ◽  
Bone Morphogenetic Protein 2 ◽  
Type I ◽  
Type Ii ◽  
Specific Expression ◽  
Morphogenetic Protein

Abstract Cbfa1/Runx2 is a transcription factor essential for bone formation and osteoblast differentiation. Two major N-terminal isoforms of Cbfa1, designated type I/p56 (PEBP2aA1, starting with the sequence MRIPV) and type II/p57 (til-1, starting with the sequence MASNS), each regulated by distinct promoters, are known. Here, we show that the type I transcript is constitutively expressed in nonosseous mesenchymal tissues and in osteoblast progenitor cells. Cbfa1 type I isoform expression does not change with the differentiation status of the cells. In contrast, the type II transcript is increased during differentiation of primary osteoblasts and is induced in osteoprogenitors and in premyoblast C2C12 cells in response to bone morphogenetic protein-2. The functional equivalence of the two isoforms in activation and repression of bone-specific genes indicates overlapping functional roles. The presence of the ubiquitous type I isoform in nonosseous cells and before bone morphogenetic protein-2 induced expression of the type II isoform suggests a regulatory role for Cbfa1 type I in early stages of mesenchymal cell development, whereas type II is necessary for osteogenesis and maintenance of the osteoblast phenotype. Our data indicate that Cbfa1 function is regulated by transcription, cellular protein levels, and DNA binding activity during osteoblast differentiation. Taken together, our studies suggest that developmental timing and cell type- specific expression of type I and type II Cbfa isoforms, and not necessarily molecular properties or sequences that reside in the N-terminus of Cbfa1, are the principal determinants of the osteogenic activity of Cbfa1.

A Histological Study on Experimental Tooth Movement into Bone Induced by Recombinant Human Bone Morphogenetic Protein-2 in Beagle Dogs

2002 ◽  
Vol 39 (4) ◽  
pp. 439-448 ◽  
Author(s):  
Tatsuo Kawamoto ◽  
Nobuyoshi Motohashi ◽  
Atsushi Kitamura ◽  
Yoshiyuki Baba ◽  
Koichiro Takahashi ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Tooth Movement ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
Control Group ◽  
Beagle Dogs ◽  
Morphogenetic Protein ◽  
Human Bone Morphogenetic Protein ◽  
Recombinant Human Bone ◽  
Experimental Tooth Movement

Objective The purpose of this preliminary study was to examine experimental tooth movement into newly generated bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2). Method After extraction of the maxillary first premolars, bone defects were surgically created in eight adult beagle dogs using a 5-mm-diameter trepan bar. According to which material was grafted into the bone defects, animals were divided into the following four groups: (1) the rhBMP-2 group in which rhBMP-2 with a poly [D,L-(lactide-co-glycolide)]/gelatin sponge complex was implanted; (2) the spongiosa group in which spongiosa from the tibia was grafted; (3) the nongrafted group in which no material was embedded; and (4) the control group in which only tooth extraction was performed. The osteoinductive activity of rhBMP-2 and tooth movement into the newly generated bone were examined by histological and morphometric comparisons of each group. Results Considerable new bone formation was observed at the grafted site both in the rhBMP-2 and in the spongiosa groups. The area of generated bone in the rhBMP-2 group was significantly greater than that in the spongiosa group. Newly generated bone, in both the rhBMP-2 and spongisosa groups, showed a similar histological response to orthodontic force as in normal alveolar bone in the control group. However, root resorption occurred on the pressure side in the rhBMP-2 group. Conclusion These results indicated that rhBMP-2 might constitute an alternative material to autogeneous bone grafting for alveolar cleft defects. Further studies regarding tooth movement into generated bone induced by rhBMP-2 are suggested.

scholarly journals Connective Tissue Growth Factor Mediates Bone Morphogenetic Protein 2-Induced Increase in Hyaluronan Production in Luteinized Human Granulosa Cells

2021 ◽  
Author(s):  
Long Bai ◽  
Hsun-Ming Chang ◽  
Yi-Min Zhu ◽  
Peter CK Leung
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Bone Morphogenetic Protein ◽  
Molecular Mechanism ◽  
Granulosa Cells ◽  
Tissue Growth ◽  
Bone Morphogenetic Protein 2 ◽  
Type I ◽  
Human Granulosa Cells ◽  
Morphogenetic Protein

Abstract Background: Hyaluronan is the main component of the cumulus-oocyte complex (COC) matrix and it maintains the basic structure of the COC during ovulation. As a member of the transforming growth factor β (TGF-β) superfamily, bone morphogenetic protein 2 (BMP2) has been identified as a critical regulator of mammalian folliculogenesis and ovulation. However, whether BMP2 can regulate the production of hyaluronan in human granulosa cells has never been elucidated.Methods: In the present study, we investigated the effect of BMP2 on the production of hyaluronan and the underlying molecular mechanism using both immortalized (SVOG) and primary human granulosa-lutein (hGL) cells. The expression of three hyaluronan synthases (including HAS1, HAS2 and HAS3) were examined following cell incubation with BMP2 at different concentrations. The concentrations of the hyaluronan cell culture medium were determined by enzyme-linked immunosorbent assay (ELISA). The TGF-β type I receptor inhibitors (dorsomorphin and DMH-1) and small interfering RNAs targeting ALK2, ALK3, ALK6 and SMAD4 were used to investigate the involvement of TGF-β type I receptor and SMAD-dependent pathway.Results: Our results showed that BMP2 treatment significantly increased the production of hyaluronan by upregulating the expression of hyaluronan synthase 2 (HAS2). In addition, BMP2 upregulates the expression of connective tissue growth factor (CTGF), which subsequently mediates the BMP2-induced increases in HAS2 expression and hyaluronan production because overexpression of CTGF enhances, whereas knockdown of CTGF reverses, these effects. Notably, using kinase inhibitor- and siRNA-mediated knockdown approaches, we demonstrated that the inductive effect of BMP2 on the upregulation of CTGF is mediated by the ALK2/ALK3-mediated SMAD-dependent signaling pathway.Conclusions: Our findings provide new insight into the molecular mechanism by which BMP2 promotes the production of hyaluronan in human granulosa cells.

scholarly journals Transplanted Bone Morphogenetic Protein/Poly(lactic-co-glycolic Acid) Delayed-release Microcysts Combined with Rat Micromorselized Bone and Collagen for Bone Tissue Engineering

2009 ◽  
Vol 37 (4) ◽  
pp. 1075-1087 ◽  
Author(s):  
Y Ji ◽  
GP Xu ◽  
JL Yan ◽  
SH Pan
Keyword(s):  
Bone Morphogenetic Protein ◽  
Glycolic Acid ◽  
Gluteus Maximus ◽  
The Other ◽  
Bone Morphogenetic Protein 2 ◽  
Bone Collagen ◽  
Delayed Release ◽  
Morphogenetic Protein ◽  
Gluteus Maximus Muscle ◽  
Autologous Bone

This study was designed to optimize the preparation of delayed-release microcysts containing bone morphogenetic protein 2 (BMP-2) combined with poly(lactic- co-glycolic acid) (PLGA) and to investigate their osteogenic properties when combined with rat autologous micromorselized bone and collagen. Rat autologous micromorselized bone, collagen and BMP-2/PLGA delayed-release microcysts were implanted in various combinations into the rat gluteus maximus muscle sack model. The following post-operative measurements were made: general observations of the implant site, histological observations, osteogenesis measurements and alkaline phosphatase activity. Autologous micromorselized bone combined with collagen and BMP-2/PLGA delayed-release microcysts demonstrated significantly superior osteogenic properties than any of the other combinations of these three components. These findings suggest that micromorselized bone combined with collagen and BMP-2/PLGA delayed-release microcysts could reduce the quantity of BMP-2 and autologous bone required for these procedures, making their use feasible in human bone restoration.

scholarly journals Bone Morphogenetic Protein-2 Antagonizes Renal Interstitial Fibrosis by Promoting Catabolism of Type I Transforming Growth Factor-β Receptors

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 727-740 ◽  
Author(s):  
Yu-Lin Yang ◽  
Yi-Shiuan Liu ◽  
Lea-Yea Chuang ◽  
Jinn-Yuh Guh ◽  
Tao-Chen Lee ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Ureteral Obstruction ◽  
Time Course ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Bone Morphogenetic Protein 2 ◽  
Type I ◽  
Morphogenetic Protein ◽  
Tgf Β1

TGF-β is a therapeutic target for renal fibrosis. Scientists have long sought ways to antagonize TGF-β to ameliorate diabetic nephropathy. Bone morphogenetic protein (BMP-2) is a member of the TGF-β superfamily and is highly regulated in the kidney. Thus, the role of BMP-2 was investigated in NRK-49F cells (rat fibroblasts). We showed that TGF-β1 induces an increase in fibronectin. Treatment with exogenous BMP-2 or pCMV-BMP-2 significantly reversed the TGF-β1-induced increase in fibronectin concomitant with a significant decrease in type I TGF-β receptors (TGF-β RI). Moreover, BMP-2 significantly shortened the half-life of TGF-β RI. These results are related to proteosomal activation because MG132, a proteasome inhibitor, abolished BMP-2-mediated degradation of TGF-β RI. This was confirmed because BMP-2 time course dependently enhanced the ubiquitination level of TGF-β RI. In addition, Smads would seem to be involved in the interaction of BMP-2 and TGF-β. We demonstrated that BMP-2 significantly reversed the TGF-β1-induced increase in pSmad2/3 and reversed the TGF-β1-induced decrease in inhibitory Smad7. Most importantly, Smad7 small interfering RNA abolished the BMP-2-induced decrease in TGF-β RI. We evaluated the clinical efficacy of BMP-2 using unilateral ureteral obstruction rats. BMP-2 was administered ip for 7 d. In the unilateral ureteral obstruction kidneys, interstitial fibrosis was prominent. However, treatment with BMP-2 dramatically reduced Masson’s trichrome staining (collagen) in the interstitial and tubular areas of the kidneys concomitantly with a reduction in TGF-β RI. These results suggest that BMP-2 acts as a novel fibrosis antagonizing cytokine partly by down-regulating TGF-β RI and Smads. Bone morphogenetic protein-2 can antagonize TGF-β-inducing cellular fibrosis by intervening post-receptors signaling, thus disclosing an application of therapeutical potential against fibrosis disorders.

Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation

1999 ◽  
Vol 112 (20) ◽  
pp. 3519-3527 ◽  
Author(s):  
T. Ebisawa ◽  
K. Tada ◽  
I. Kitajima ◽  
K. Tojo ◽  
T.K. Sampath ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Osteoblast Differentiation ◽  
Transforming Growth Factor ◽  
C2c12 Cells ◽  
Nuclear Accumulation ◽  
Type I ◽  
Type Ii ◽  
Weakly Bound ◽  
Bmp Receptors ◽  
Morphogenetic Protein

Bone morphogenetic protein (BMP)-6 is a member of the transforming growth factor (TGF)-(β) superfamily, and is most similar to BMP-5, osteogenic protein (OP)-1/BMP-7, and OP-2/BMP-8. In the present study, we characterized the endogenous BMP-6 signaling pathway during osteoblast differentiation. BMP-6 strongly induced alkaline phosphatase (ALP) activity in cells of osteoblast lineage, including C2C12 cells, MC3T3-E1 cells, and ROB-C26 cells. The profile of binding of BMP-6 to type I and type II receptors was similar to that of OP-1/BMP-7 in C2C12 cells and MC3T3-E1 cells; BMP-6 strongly bound to activin receptor-like kinase (ALK)-2 (also termed ActR-I), together with type II receptors, i.e. BMP type II receptor (BMPR-II) and activin type II receptor (ActR-II). In addition, BMP-6 weakly bound to BMPR-IA (ALK-3), to which BMP-2 also bound. In contrast, binding of BMP-6 to BMPR-IB (ALK-6), and less efficiently to ALK-2 and BMPR-IA, together with BMPR-II was detected in ROB-C26 cells. Intracellular signalling was further studied using C2C12 and MC3T3-E1 cells. Among the receptor-regulated Smads activated by BMP receptors, BMP-6 strongly induced phosphorylation and nuclear accumulation of Smad5, and less efficiently those of Smad1. However, Smad8 was constitutively phosphorylated, and no further phosphorylation or nuclear accumulation of Smad8 by BMP-6 was observed. These findings indicate that in the process of differentiation to osteoblasts, BMP-6 binds to ALK-2 as well as other type I receptors, and transduces signals mainly through Smad5 and possibly through Smad1.

scholarly journals Statin-induced Ras Activation Integrates the Phosphatidylinositol 3-Kinase Signal to Akt and MAPK for Bone Morphogenetic Protein-2 Expression in Osteoblast Differentiation

2006 ◽  
Vol 282 (7) ◽  
pp. 4983-4993 ◽  
Author(s):  
Nandini Ghosh-Choudhury ◽  
Chandi Charan Mandal ◽  
Goutam Ghosh Choudhury
Keyword(s):  
Bone Morphogenetic Protein ◽  
Osteoblast Differentiation ◽  
Dominant Negative ◽  
Bone Morphogenetic Protein 2 ◽  
Regulatory Subunit ◽  
Type I ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Morphogenetic Protein ◽  
Phosphatidylinositol 3

Lovastatin promotes osteoblast differentiation by increasing bone morphogenetic protein-2 (BMP-2) expression. We demonstrate that lovastatin stimulates tyrosine phosphorylation of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K), leading to an increase in its kinase activity in osteoblast cells. Inhibition of PI3K ameliorated expression of the osteogenic markers alkaline phosphatase, type I collagen, osteopontin, and BMP-2. Expression of dominant-negative PI3K and PTEN, an inhibitor of PI3K signaling, significantly attenuated lovastatin-induced transcription of BMP-2. Akt kinase was also activated in a PI3K-dependent manner. However, our data suggest involvement of an additional signaling pathway. Lovastatin-induced Erk1/2 activity contributed to BMP-2 transcription. Inhibition of PI3K abrogated Erk1/2 activity in response to lovastatin, indicating the presence of a signal relay between them. We provide, as a mechanism of this cross-talk, the first evidence that lovastatin stimulates rapid activation of Ras, which associates with and activates PI3K in the plasma membrane, which in turn regulates Akt and Erk1/2 to induce BMP-2 expression for osteoblast differentiation.

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