Weekly intra-articular injections of bone morphogenetic protein-7 inhibits osteoarthritis progression

Hayashi, Masaya; Muneta, Takeshi; Ju, Young-Jin; Mochizuki, Takashi; Sekiya, Ichiro

doi:10.1186/ar2521

Cited by 64 publications

(52 citation statements)

References 22 publications

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“…Dimitrios Iliopoulos et al . demonstrated in OA miR‐22 directly inhibited the expression of BMP‐7 and PPARA, which led to the increased expression of IL‐1 and MMP‐13 and subsequent chondrocytes degeneration and matrix degradation 23. Yamasaki et al .…”

Section: Discussionmentioning

confidence: 99%

MiR‐29b‐3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN

Chen

Wang

et al. 2017

J Cellular Molecular Medi

110

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This study was aimed to explore the role of miR‐29b‐3p and PGRN in chondrocyte apoptosis and the initiation and progress of osteoarthritis (OA). Both miR‐29b‐3p and PGRN were up‐regulated in cartilage tissue from patients with OA. Transfection of miR‐29b‐3p mimic into rat primary chondrocytes and SW1353 chondrosarcoma cells significantly suppressed PGRN expression and release, induced apoptosis, inhibited proliferation and scratch wound closure. By contrast, transfection of miR‐29b‐3p inhibitor exhibited the opposite effects. Moreover, the expression and secretion of cartilaginous degeneration‐related molecules were also altered by miR‐29b‐3p. Luciferase reporter gene assay showed rat GRN mRNA is directly targeted and repressed by miR‐29b‐3p. The fact that recombinant PGRN or shPGRN‐mediated PGRN interference abolished miR‐29b‐3p mimic‐induced cell apoptosis and growth inhibition suggested miR‐29b‐3p affect the cellular functions of chondrocyte through regulating PGRN expression. In vivo, joint cavity injection of miR‐29b‐3p antagomir prior to surgical induction of OA significantly suppressed the upregulation of miR‐29b‐3p, whereas further promoted the increased expression of PGRN. Articular chondrocytes apoptosis and cartilage loss in the knee joint of surgically induced OA rats were also ameliorated by the injection of miR‐29b‐3p antagomir, demonstrated by TUNEL and safranin O‐fast green staining. This work showed miR‐29b‐3p facilitates chondrocyte apoptosis and OA by targeting PGRN, and miR‐29b‐3p or PGRN may be the potential target for OA treatments.

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Section: Discussionmentioning

confidence: 99%

MiR‐29b‐3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN

Chen

Wang

et al. 2017

J Cellular Molecular Medi

110

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“…3 During ACL reconstruction, cartilage degeneration was also observed at high rates, 4 and ACL transection is one of the most widely used animal models for cartilage degeneration. 5 Therefore, there seems to be three intercorrelations among three conditions; ACL injury, cartilage degeneration, and MSCs in SF. The first purpose of this study was to investigate a direct relation between the number of MSCs in SF and cartilage degeneration in the ACL injured knees.…”

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confidence: 99%

Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis

Sekiya

Ojima

Suzuki

et al. 2011

Journal Orthopaedic Research

Self Cite

188

174

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We investigated whether mesenchymal stem cells (MSCs) in synovial fluid (SF) increased in the knee with degenerated cartilage and osteoarthritis. SF was obtained from the knee joints of 22 patients with anterior cruciate ligament (ACL) injury during ACL reconstruction, and cartilage degeneration was evaluated arthroscopically. SF was also obtained from the knee joints of 6 healthy volunteers, 20 patients with mild osteoarthritis, and 26 patients with severe osteoarthritis, in which the grading was evaluated radiographically. The cell component in the SF was cultured for analyses. Synovium (SYN) and bone marrow (BM) were also harvested during total knee arthroplasties. The MSC number in SF was correlated with the cartilage degeneration score evaluated by arthroscopy. The MSC number in the SF was hardly noticed in normal volunteers, but it increased in accordance with the grading of osteoarthritis. Though no significant differences were observed regarding surface epitopes, or differentiation potentials, the morphology and gene profiles in SF MSCs were more similar to those in SYN MSCs than in BM MSCs. We listed 20 genes which were expressed higher in both SYN MSCs and SF MSCs than in BM MSCs, and 3 genes were confirmed by quantitative RT-PCR. MSCs in SF increased along with degenerated cartilage and osteoarthritis. ß

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“…BMPs bind and signal through serine/threonine kinase receptors (8)(9)(10). BMP-7 binding to the BMP receptor type IB leads to receptor dimerization so that the type I receptor phosphorylates Smad1/5/8 and stimulates expression of genes that promote cartilage repair (7,11) and may protect against OA (6,12). The BMP antagonist noggin is a secreted protein that interacts with heparan sulfate proteoglycans (HSPGs) at the cell membrane where it binds and prevents BMP-2, -4, -6, and -7 from activating their receptors (13).…”

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confidence: 99%

Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways

Otsuki¹,

Hanson

Miyaki³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

113

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The balance between anabolic and catabolic signaling pathways is critical in maintaining cartilage homeostasis and its disturbance contributes to joint diseases such as osteoarthritis (OA). A unique mechanism that modulates the activity of cell signaling pathways is controlled by extracellular heparan endosulfatases Sulf-1 and Sulf-2 (Sulfs) that are overexpressed in OA cartilage. This study addressed the role of Sulfs in cartilage homeostasis and in regulating bone morphogenetic protein (BMP)/Smad and fibroblast growth factor (FGF)/Erk signaling in articular cartilage. Spontaneous cartilage degeneration and surgically induced OA were significantly more severe in Sulf-1 −/− and Sulf-2 −/− mice compared with wild-type mice. MMP-13, ADAMTS-5, and the BMP antagonist noggin were elevated whereas col2a1 and aggrecan were reduced in cartilage and chondrocytes from Sulf −/− mice. Articular cartilage and cultured chondrocytes from Sulf −/− mice showed reduced Smad1 protein expression and Smad1/5 phosphorylation, whereas Erk1/2 phosphorylation was increased. In human chondrocytes, Sulfs siRNA reduced Smad phosphorylation but enhanced FGF-2-induced Erk1/2 signaling. These findings suggest that Sulfs simultaneously enhance BMP but inhibit FGF signaling in chondrocytes and maintain cartilage homeostasis. Approaches to correct abnormal Sulf expression have the potential to protect against cartilage degradation and promote cartilage repair in OA.artilage homeostasis is controlled by extracellular factors such as mechanical loading, cytokines, and growth factors that are translated by intracellular signaling pathways to changes in cell survival, activation, and differentiation. Abnormal activation of these signaling pathways during development results in skeletal dysplasias and, in mature joints, leads to osteoarthritis (OA) (1).Bone morphogenetic proteins (BMPs) regulate various stages of cartilage and bone development (2-4), promote chondrogenesis from mesenchymal stem cells, and stimulate cartilage repair (5-7). BMPs bind and signal through serine/threonine kinase receptors (8-10). BMP-7 binding to the BMP receptor type IB leads to receptor dimerization so that the type I receptor phosphorylates Smad1/5/8 and stimulates expression of genes that promote cartilage repair (7, 11) and may protect against OA (6, 12). The BMP antagonist noggin is a secreted protein that interacts with heparan sulfate proteoglycans (HSPGs) at the cell membrane where it binds and prevents BMP-2, -4, -6, and -7 from activating their receptors (13).In contrast, fibroblast growth factor-2 (FGF-2) stimulates catabolic responses in chondrocytes by activating Erk1/2 (14). Models have been proposed to describe the interaction of HSPGs with FGFs and their receptors, yet the precise molecular details remain to be determined (15). It has been established that FGF signaling requires HSPGs to form stable ligand/receptor complexes, apparently by protecting the FGF ligand from proteolytic degradation and by enhancing and stabilizing cell surface ligand/receptor ...

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Weekly intra-articular injections of bone morphogenetic protein-7 inhibits osteoarthritis progression

Abstract: Introduction We investigated the ability of a weekly intraarticular injection of bone morphogenetic protein (BMP)-7 to prevent osteoarthritis in rabbits with anterior cruciate ligament transections.

Cited by 64 publications

References 22 publications

MiR‐29b‐3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN

MiR‐29b‐3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN

Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis

Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways

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