The Effect of Bone Morphogenetic Protein-2 on Rat Intervertebral Disc Cells in Vitro

Yoon, S. Tim; Kh, Kim; Li, Jun; Park, Jin-Soo; Akamaru, Tomoyuki; Elmer, William A.; Hutton, William

doi:10.1097/01.brs.0000083204.44190.34

Cited by 123 publications

(28 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Growth factors shift the metabolic status of IVD cells from the catabolic state to the anabolic state to regenerate degenerative discs [10]. Various growth factors have been demonstrated to stimulate the proliferation of and matrix synthesis by IVD cells in vitro , including transforming growth factor-β (TGF-β), epidermal growth factor (EGF) [13,14], insulin-like growth factor-1 (IGF-1) [15], growth and differentiation factor-5 (GDF-5) [16,17], osteogenic protein-1 (OP-1) [18,19] and bone morphogenetic protein-2 (BMP-2) [20,21]. Furthermore, in vivo , OP-1 and GDF-5 have been determined to induce the restoration of disc height and to increase the proteoglycan (PG) content in NP [22,23,24].…”

Section: Introductionmentioning

confidence: 99%

Growth and Differentiation Factor-5 Contributes to the Structural and Functional Maintenance of the Intervertebral Disc

Feng

Liu

Yang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Intervertebral disc degeneration (IDD) is a widely recognized contributor to low back pain (LBP). The Prevention or reversal of IDD is a potential treatment for LBP. Unfortunately, current treatments for IDD are aimed at relieving symptoms rather than regenerating disc structure or function. Recently, the injection of growth factors and mesenchymal stem cell (MSC) transplantation have been shown to be promising biological therapies for IDD. Growth factors stimulate the proliferation of and matrix synthesis by intervertebral disc (IVD) cells, leading to the regeneration of degenerative discs. Growth factors, hypoxia and co-culture with nucleus pulposus (NP) cells induce MSCs to differentiate toward an NP-like phenotype, which can increase the number of functional cells in the IVD or enhance the function of endogenous disc cells to facilitate IVD regeneration. Therefore, the emerging roles of growth factors in IVD regeneration have piqued the interest of researchers. Growth factors including transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), insulin-like growth factor-1 (IGF-1) and growth and differentiation factor-5 (GDF-5), among others, have been demonstrated to enhance anabolism in IVD cells and to induce NP-like differentiation of MSCs. However, the injection of TGF, IGF and FGF into human IVDs may induce unwanted blood vessel ingrowth, which accelerates the process of IDD, the injection of GDF-5 may not have the same effect. This finding suggests that GDF-5 is a preferable growth factor for use in IDD treatment compared with TGF, IGF and FGF. The GDF-5 gene is one of the few growth factor genes that have been found to be associated with IDD thus far; moreover, the GDF-5 gene defects lead to collagen and proteoglycan abnormalities in discs in mice, suggesting that GDF-5 contributes to the structural and functional maintenance of the IVD. This review is focused on the functions of GDF-5 in the IVD and on the association between GDF-5 and a genetic predisposition to IDD. The effects of GDF-5 on IVD regeneration and on MSC differentiation are also discussed. GDF-5 plays a crucial role in the pathogenesis of IDD and is a promising therapeutic agent for IDD. Additionally, stem cell transplantation has been shown to be a promising biological therapy for IDD.

show abstract

Section: Introductionmentioning

confidence: 99%

Growth and Differentiation Factor-5 Contributes to the Structural and Functional Maintenance of the Intervertebral Disc

Feng

Liu

Yang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Besides their ability to induce collagen and PG production in AF cells [9,10,11,12,13] they may also have an impact on AF ossification. It was reported that in concentrations of 1 µg/mL BMP2 and TGFβ3 induce ossification in the AF in an intervertebral disc rabbit explant model.…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular matrix (ECM) PGs play an important functional role due to their high water-binding capacity in the disc [8]. Factors such as BMP2 [9], BMP7 [10], and BMP14 [11] led to increased PG synthesis in various animal cell cultures in vitro or to an increase in AF tissue thickness in animal models. In a comparative in vitro study in which various BMPs were adenovirally transduced into bovine AF cells, almost all BMPs were found to be effective in increasing PG content and collagen type II formation.…”

Section: Introductionmentioning

confidence: 99%

Chemokine CCL25 Induces Migration and Extracellular Matrix Production of Anulus Fibrosus-Derived Cells

Stich

Möller

Čabraja

et al. 2018

IJMS

View full text Add to dashboard Cite

Intervertebral disc degeneration is a major source of back pain. For intervertebral disc regeneration after herniation a fast closure of anulus fibrosus (AF) defects is crucial. Here, the use of the C-C motif chemokine ligand 25 (CCL)25 in comparison to differentiation factors such as transforming growth factor (TGF)β3, bone morphogenetic protein (BMP)2, BMP7, BMP12, and BMP14 (all in concentrations of 10, 50 and 100 ng/mL) was tested in an in vitro micro mass pellet model with isolated and cultivated human AF-cells (n = 3) to induce and enhance AF-matrix formation. The pellets were differentiated (serum-free) with supplementation of the factors. After 28 days all used factors induced proteoglycan production (safranin O staining) and collagen type I production (immunohistochemical staining) in at least one of the tested concentrations. Histomorphometric scoring revealed that TGFβ3 delivered the strongest induction of proteoglycan production in all three concentrations. Furthermore, it was the only factor able to facilitate collagen type II production, even higher than in native tissue samples. CCL25 was also able to induce proteoglycan and collagen type I production comparable to several BMPs. CCL25 could additionally induce migration of AF-cells in a chemotaxis assay and therefore possibly aid in regeneration processes after disc herniation by recruiting AF-cells.

show abstract

“…BMP-2 is particularly important for the generation of mature osteoblasts in vivo , and induces the signaling cascades leading to cytoskeletal rearrangement [21]. Moreover, BMP-2 has also been shown to be effective in stimulating proteoglycan production [22]. Considering the important role of osteoblast differentiation in OS, we measured the expression of both genes upon infection.…”

Section: Discussionmentioning

confidence: 99%

LIM Mineralization Protein-1 Inhibits the Malignant Phenotypes of Human Osteosarcoma Cells

Liu

Zhang

et al. 2014

IJMS

View full text Add to dashboard Cite

Osteosarcoma (OS), also known as osteogenic sarcoma, is the most common primary malignancy of bone tumor in children and adolescents. However, its underlying molecular pathogenesis is still only vaguely understood. Recently, LIM mineralization protein-1 (LMP-1) was reported to be an essential positive regulator of osteoblast differentiation. In the present study, we found that the expression of LMP-1 is downregulated in OS tissues compared with adjacent normal tissues. Moreover, we restored the expression of LMP-1 through a recombinant adenovirus. Overexpression of LMP-1 inhibited cell proliferation and invasion, arrested cell cycle progression, and induced apoptosis in vitro. Finally, ectopic LMP-1 expression suppressed the expression of Runx2 and BMP-2 in OS cells. These data demonstrate that LMP-1 is an essential tumor suppressor in the OS pathological process, which will provide a new opportunity for discovering and identifying novel effective treatment strategies.

show abstract

The Effect of Bone Morphogenetic Protein-2 on Rat Intervertebral Disc Cells in Vitro

Cited by 123 publications

References 44 publications

Growth and Differentiation Factor-5 Contributes to the Structural and Functional Maintenance of the Intervertebral Disc

Growth and Differentiation Factor-5 Contributes to the Structural and Functional Maintenance of the Intervertebral Disc

Chemokine CCL25 Induces Migration and Extracellular Matrix Production of Anulus Fibrosus-Derived Cells

LIM Mineralization Protein-1 Inhibits the Malignant Phenotypes of Human Osteosarcoma Cells

Contact Info

Product

Resources

About