Role of BMP-2 and OP-1 (BMP-7) in programmed cell death and skeletogenesis during chick limb development

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1109-1117 ◽  
Author(s):  
D. Macias ◽  
Y. Ganan ◽  
T.K. Sampath ◽  
M.E. Piedra ◽  
M.A. Ros ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Limb Development ◽  
Transforming Growth Factor ◽  
Limb Bud ◽  
Bone Morphogenetic Protein 2 ◽  
Joint Formation ◽  
Morphogenetic Protein ◽  
Limb Morphogenesis ◽  
Complementary Pattern ◽  
In Situ Hybridizations

Bone Morphogenetic Protein 2 (BMP-2) and Osteogenic Protein 1 (OP-1, also termed BMP-7) are members of the transforming growth factor beta superfamily. In the present study, we have analyzed the effects of administering them locally at different stages and locations of the chick limb bud using heparin beads as carriers. Our results show that these BMPs are potent apoptotic signals for the undifferentiated limb mesoderm but not for the ectoderm or the differentiating chondrogenic cells. In addition, they promote intense radial growth of the differentiating cartilages and disturb the formation of joints accompanied by alterations in the pattern of Indian hedgehog and ck-erg expression. Interestingly, the effects of these two BMPs on joint formation were found to be different. While the predominant effect of BMP-2 is alteration in joint shape, OP-1 is a potent inhibitory factor for joint formation. In situ hybridizations to check whether this finding was indicative of specific roles for these BMPs in the formation of joints revealed a distinct and complementary pattern of expression of these genes during the formation of the skeleton of the digits. While Op-1 exhibited an intense expression in the perichondrium of the developing cartilages with characteristic interruptions in the zones of joint formation, Bmp-2 expression was a positive marker for the articular interspaces. These data suggest that, in addition to the proposed role for BMP-2 and OP-1 in the establishment of the anteroposterior axis of the limb, they may also play direct roles in limb morphogenesis: (i) in regulating the amount and spatial distribution of the undifferentiated prechondrogenic mesenchyme and (ii) in controlling the location of the joints and the diaphyses of the cartilaginous primordia of the long bones once the chondrogenic aggregates are established.

scholarly journals Chondrogenic Differentiation from Induced Pluripotent Stem Cells Using Non-Viral Minicircle Vectors

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 582 ◽  
Author(s):  
Yeri Alice Rim ◽  
Yoojun Nam ◽  
Narae Park ◽  
Hyerin Jung ◽  
Kijun Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Transforming Growth Factor Beta ◽  
Pluripotent Stem Cells ◽  
Transforming Growth Factor ◽  
Cartilage Regeneration ◽  
Bone Morphogenetic Protein 2 ◽  
Viral Gene ◽  
Morphogenetic Protein ◽  
Induced Pluripotent

Human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently, chondrogenesis using human pluripotent stem cells (hiPSCs) is accomplished using human recombinant growth factors. Here, we differentiate hiPSCs into chondrogenic pellets using minicircle vectors. Minicircles are a non-viral gene delivery system that can produce growth factors without integration into the host genome. We generated minicircle vectors containing bone morphogenetic protein 2 (BMP2) and transforming growth factor beta 3 (TGFβ3) and delivered them to mesenchymal stem cell-like, hiPSC-derived outgrowth (OG) cells. Cell pellets generated using minicircle-transfected OG cells successfully differentiated into the chondrogenic lineage. The implanted minicircle-based chondrogenic pellets recovered the osteochondral defects in rat models. This work is a proof-of-concept study that describes the potential application of minicircle vectors in cartilage regeneration using hiPSCs.

scholarly journals Heterotopic ossification in a patient with diffuse idiopathic skeletal hyperostosis: Input from histological findings

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Caterina Licini ◽  
Luca Farinelli ◽  
Giorgia Cerqueni ◽  
Andrell Hosein ◽  
Saverio Marchi ◽  
...  
Keyword(s):  
Heterotopic Ossification ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Diffuse Idiopathic Skeletal Hyperostosis ◽  
Bone Morphogenetic Protein 2 ◽  
Endochondral Bone Formation ◽  
Surgical Trauma ◽  
Endochondral Bone ◽  
Morphogenetic Protein ◽  
High Incidence

A high incidence of heterotopic ossification (HO) has been reported in patients with diffuse idiopathic skeletal hyperostosis (DISH), a metabolic disease characterized by calcifications of entheses at spine and peripheral sites. We performed histological and immunohistochemical analyses in five different HO sites in a patient with DISH to study a possible mutual interaction of bone morphogenetic protein 2 (BMP-2), transforming growth factor beta (TGF-β), and decorin, crucial for bone mass increasing, matrix calcification, and endochondral bone formation. We speculated that the surgical trauma triggered HO, inducing TGF-β release at the lesion site. TGF-β recruits osteoblast precursor cells and determines the overexpression of BMP-2 in the surrounding skeletal muscle, inducing a further osteogenic differentiation, contributing to HO onset.

175. THE ROLE OF PROPROTEIN CONVERTASE 6 DURING DECIDUALIZATION: REGULATION OF BONE MORPHOGENETIC PROTEIN 2 ACTIVATION

2009 ◽  
Vol 21 (9) ◽  
pp. 93
Author(s):  
S. Heng ◽  
B. Hardman ◽  
S. Paule ◽  
H. Singh ◽  
G. Nie
Keyword(s):  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Active Form ◽  
Bone Morphogenetic Protein 2 ◽  
Tgf Beta ◽  
Proprotein Convertase ◽  
Morphogenetic Protein ◽  
Total Inhibition

Proprotein convertase 5/6 (PC6), a member of the proprotein convertase (PC) family, is a critical endometrial factor for implantation. PC6 is up-regulated in the endometrium specifically at implantation in association with epithelial differentiation (in human and monkey) and stromal cell decidualization (in the mouse, human and monkey). PC6 is the only PC member that was significantly up-regulated during decidualization. Knockdown of PC6 inhibits decidualization. PCs function by converting a range of important precursor proteins into their bioactive forms. One group of such proteins is the transforming growth factor beta (TGF-beta) superfamily proteins. They are first synthesized as larger biologically inactive precursors, and then are processed by PCs into their active forms. Bone morphogenetic protein 2 (BMP2) is a TGF-beta superfamily member and demonstrated to be essential for decidualization. We hypothesized that BMP2 is one of the proteins that PC6 activates during decidualization. Freshly isolated stromal cells from human endometrium were decidualized in culture with and without inhibition of PC6 activity. The full-length (precursor, non-active) and processed (activated) forms of BMP2 were determined in cellular lysates and media. The precursor form of BMP2 was reduced whereas the active form was increased during decidualization. Inhibition of PC6 activity inhibited decidualization, and this inhibition was accompanied by a total inhibition of the production of active BMP2. To further confirm the role of PC6 in activating BMP2 in decidualization, active BMP2 was added into cells and the decidualization arrest caused by PC6 inhibition was partially rescued. This study demonstrated that PC6 regulates decidualization by activating molecules such as BMP2 that are essential for decidualization.

scholarly journals Bone Morphogenetic Protein-2 in Development and Bone Homeostasis

2020 ◽  
Vol 8 (3) ◽  
pp. 19 ◽  
Author(s):  
Daniel Halloran ◽  
Hilary W. Durbano ◽  
Anja Nohe
Keyword(s):  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Bone Morphogenetic Protein 2 ◽  
Osteogenic Potential ◽  
Bone Homeostasis ◽  
Spinal Fusion Surgery ◽  
Morphogenetic Protein ◽  
Related Transcription Factor

Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the Transforming Growth Factor-Beta (TGF-β) superfamily. These proteins are essential to many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Specifically, within the BMP family, Bone Morphogenetic Protein-2 (BMP-2) was the first BMP to be characterized and has been well-studied. BMP-2 has important roles during embryonic development, as well as bone remodeling and homeostasis in adulthood. Some of its specific functions include digit formation and activating osteogenic genes, such as Runt-Related Transcription Factor 2 (RUNX2). Because of its diverse functions and osteogenic potential, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery, tibial shaft repair, and maxillary sinus reconstructive surgery. However, shortly after initial injections of rhBMP-2, several adverse complications were reported, and alternative therapeutics have been developed to limit these side-effects. As the clinical application of BMP-2 is largely implicated in bone, we focus primarily on its role in bone. However, we also describe briefly the role of BMP-2 in development. We then focus on the structure of BMP-2, its activation and regulation signaling pathways, BMP-2 clinical applications, and limitations of using BMP-2 as a therapeutic. Further, this review explores other potential treatments that may be useful in treating bone disorders.

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