scholarly journals Blockage of bone morphogenetic protein signalling counteracts hypertrophy in a human osteoarthritic micro-cartilage model

2020 ◽  
Vol 133 (23) ◽  
pp. jcs249094 ◽  
Author(s):  
Shikha Chawla ◽  
Majoska H. M. Berkelaar ◽  
Boris Dasen ◽  
Christine Halleux ◽  
Sabine Guth-Gundel ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Selective Inhibition ◽  
Type I ◽  
Mesenchymal Progenitors ◽  
Morphogenetic Protein ◽  
Cartilage Extracellular Matrix ◽  
Embryonic Cartilage ◽  
Oa Chondrocytes ◽  
Bmp Signalling

ABSTRACTBone morphogenetic protein (BMP) signalling plays a significant role during embryonic cartilage development and has been associated with osteoarthritis (OA) pathogenesis, being in both cases involved in triggering hypertrophy. Inspired by recent findings that BMP inhibition counteracts hypertrophic differentiation of human mesenchymal progenitors, we hypothesized that selective inhibition of BMP signalling would mitigate hypertrophic features in OA cartilage. First, a 3D in vitro OA micro-cartilage model was established using minimally expanded OA chondrocytes that was reproducibly able to capture OA-like hypertrophic features. BMP signalling was then restricted by means of two BMP receptor type I inhibitors, resulting in reduction of OA hypertrophic traits while maintaining synthesis of cartilage extracellular matrix. Our findings open potential pharmacological strategies for counteracting cartilage hypertrophy in OA and support the broader perspective that key signalling pathways known from developmental processes can guide the understanding, and possibly the mitigation, of adult pathological features.

Bone Morphogenetic Protein-2 Inhibits Differentiation and Mineralization of Cementoblasts in vitro

2003 ◽  
Vol 82 (1) ◽  
pp. 23-27 ◽  
Author(s):  
M. Zhao ◽  
J.E. Berry ◽  
M.J. Somerman
Keyword(s):  
Bone Morphogenetic Protein ◽  
Type I Collagen ◽  
Bone Morphogenetic Protein 2 ◽  
Nodule Formation ◽  
Type I ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Morphogenetic Protein ◽  
Regenerative Therapies

As an approach for improving the outcome and predictability of periodontal regenerative therapies, we have focused on determining the responses of cells within the local environment to putative regenerative factors. This study examined the effects of bone morphogenetic protein-2 (BMP-2) on murine cementoblasts in vitro. Northern blot analysis indicated that BMP-2 decreased mRNA levels of bone sialoprotein and type I collagen dose-dependently (10–300 ng/mL). At low doses, up to 100 ng/mL, BMP-2 had no effect on transcripts for osteocalcin and osteopontin, whereas at 300 ng/mL, BMP-2 greatly increased expression of these two genes. BMP-2 also inhibited cementoblast-mediated mineral nodule formation in a dose-dependent manner (inhibition was noted at 10 ng/mL). Noggin reversed the effects of BMP-2 on gene expression and on mineralization. These findings reflect the diverse responses of periodontal cells to BMP-2 and highlight the need to consider the complexity of factors involved in designing predictable regenerative therapies.

scholarly journals Is NO the Answer? The Nitric Oxide Pathway Can Support Bone Morphogenetic Protein 2 Mediated Signaling

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1273 ◽  
Author(s):  
Christopher Differ ◽  
Franka Klatte-Schulz ◽  
Nicole Bormann ◽  
Susann Minkwitz ◽  
Petra Knaus ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fracture Healing ◽  
Bone Morphogenetic Protein ◽  
Clinical Importance ◽  
Bmp Signaling ◽  
Bone Morphogenetic Protein 2 ◽  
Type I ◽  
Positive Effects ◽  
Morphogenetic Protein

The growth factor bone morphogenetic protein 2 (BMP2) plays an important role in bone development and repair. Despite the positive effects of BMP2 in fracture healing, its use is associated with negative side effects and poor cost effectiveness, partly due to the large amounts of BMP2 applied. Therefore, reduction of BMP2 amounts while maintaining efficacy is of clinical importance. As nitric oxide (NO) signaling plays a role in bone fracture healing and an association with the BMP2 pathway has been indicated, this study aimed to investigate the relationship of BMP2 and NO pathways and whether NO can enhance BMP2-induced signaling and osteogenic abilities in vitro. To achieve this, the stable BMP reporter cell line C2C12BRELuc was used to quantify BMP signaling, and alkaline phosphatase (ALP) activity and gene expression were used to quantify osteogenic potency. C2C12BRELuc cells were treated with recombinant BMP2 in combination with NO donors and substrate (Deta NONOate, SNAP & L-Arginine), NOS inhibitor (LNAME), soluble guanylyl cyclase (sGC) inhibitor (LY83583) and activator (YC-1), BMP type-I receptor inhibitor (LDN-193189), or protein kinase A (PKA) inhibitor (H89). It was found that the NOS enzyme, direct NO application, and sGC enhanced BMP2 signaling and improved BMP2 induced osteogenic activity. The application of a PKA inhibitor demonstrated that BMP2 signaling is enhanced by the NO pathway via PKA, underlining the capability of BMP2 in activating the NO pathway. Collectively, this study proves the ability of the NO pathway to enhance BMP2 signaling.

scholarly journals Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation

2013 ◽  
Vol 210 (12) ◽  
pp. 2597-2610 ◽  
Author(s):  
Nighat Yasmin ◽  
Thomas Bauer ◽  
Madhura Modak ◽  
Karin Wagner ◽  
Christopher Schuster ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Prenatal Development ◽  
Langerhans Cell ◽  
Type I ◽  
Blood Monocytes ◽  
Bone Morphogenetic Protein 7 ◽  
Morphogenetic Protein ◽  
Tgf Β1

Human Langerhans cell (LC) precursors populate the epidermis early during prenatal development and thereafter undergo massive proliferation. The prototypic antiproliferative cytokine TGF-β1 is required for LC differentiation from human CD34+ hematopoietic progenitor cells and blood monocytes in vitro. Similarly, TGF-β1 deficiency results in LC loss in vivo. However, immunohistology studies revealed that human LC niches in early prenatal epidermis and adult basal (germinal) keratinocyte layers lack detectable TGF-β1. Here we demonstrated that these LC niches express high levels of bone morphogenetic protein 7 (BMP7) and that Bmp7-deficient mice exhibit substantially diminished LC numbers, with the remaining cells appearing less dendritic. BMP7 induces LC differentiation and proliferation by activating the BMP type-I receptor ALK3 in the absence of canonical TGF-β1–ALK5 signaling. Conversely, TGF-β1–induced in vitro LC differentiation is mediated via ALK3; however, co-induction of ALK5 diminished TGF-β1–driven LC generation. Therefore, selective ALK3 signaling by BMP7 promotes high LC yields. Within epidermis, BMP7 shows an inverse expression pattern relative to TGF-β1, the latter induced in suprabasal layers and up-regulated in outer layers. We observed that TGF-β1 inhibits microbial activation of BMP7-generated LCs. Therefore, TGF-β1 in suprabasal/outer epidermal layers might inhibit LC activation, resulting in LC network maintenance.

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