Midkine Deficiency Increases the Anabolic Response of Cortical Bone to Mechanical Loading

Liedert, Astrid; Mattausch, Laura; Vogele, Daniel; Pahl, Marcus; Bindl, Ronny; Neunaber, Claudia; Schinke, Thorsten; Harroch, Sheila; Amling, Michael; Ignatius, Anita

doi:10.1016/s0021-9290(12)70092-1

Cited by 2 publications

(8 citation statements)

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“…As an MK receptor, PTPζ has been shown to be involved in migration of embryonic neurons (Maeda et al ., ) and UMR106 osteoblast‐like cells (Qi et al ., ), survival of embryonic neurons (Sakaguchi et al ., ) and B cells (Cohen et al ., ), and suppression of the proliferation of osteoblasts (Liedert et al ., ). Consistent with the important role of PTPζ in MK signalling, genetic analysis suggests that Drosophila miple functions also through PTPζ (Munoz‐Soriano et al ., ).…”

Section: Mk Signallingmentioning

confidence: 97%

“…Dephosphorylation of β‐catenin is a critical step in canonical Wnt signalling. In osteoblasts, MK has been shown to inhibit osteoblast proliferation by interfering in Wnt signalling by inhibiting PTPζ‐mediated dephosphorylation of β‐catenin (Liedert et al ., ).…”

Section: Mk Signallingmentioning

confidence: 97%

“…Concerning mesoderm remodelling, MK stimulates adipocyte differentiation (Cernkovich et al ., ), chondrogenesis (Ohta et al ., ) and osteoclast differentiation (Maruyama et al ., ), and promotes the differentiation and suppresses the proliferation of osteoblasts (Liedert et al ., ).…”

Section: Mk In Development and Reproductionmentioning

confidence: 99%

“…After ligand receptor interactions of PTPζ with MK or PTN, tyrosine phosphorylation is increased in cytoplasmic signalling molecules such as β‐catenin, (Meng et al ., ; Liedert et al ., ), β‐adducin (Pariser et al ., 2005a), Fyn (Pariser et al ., 2005b), Syk (Cohen et al ., ) and Akt (Qi et al ., ; Cohen et al ., ). It is likely that after ligand stimulation, PTPζ is dimerized, leading to inactivation of the intracellular phosphatase domain, and results in increased tyrosine phosphorylation.…”

Section: Mk Signallingmentioning

confidence: 99%

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Structure and function of midkine as the basis of its pharmacological effects

Muramatsu

2014

British J Pharmacology

106

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Midkine (MK) is a heparin-binding growth factor or cytokine and forms a small protein family, the other member of which is pleiotrophin. MK enhances survival, migration, cytokine expression, differentiation and other activities of target cells. MK is involved in various physiological processes, such as development, reproduction and repair, and also plays important roles in the pathogenesis of inflammatory and malignant diseases. MK is largely composed of two domains, namely a more N-terminally located N-domain and a more C-terminally located C-domain. Both domains are basically composed of three antiparallel β-sheets. In addition, there are short tails in the N-terminal and C-terminal sides and a hinge connecting the two domains. Several membrane proteins have been identified as MK receptors: receptor protein tyrosine phosphatase Z1 (PTPζ), low-density lipoprotein receptor-related protein, integrins, neuroglycan C, anaplastic lymphoma kinase and Notch-2. Among them, the most established one is PTPζ. It is a transmembrane tyrosine phophatase with chondroitin sulfate, which is essential for high-affinity binding with MK. PI3K and MAPK play important roles in the downstream signalling system of MK, while transcription factors affected by MK signalling include NF-κB, Hes-1 and STATs. Because of the involvement of MK in various physiological and pathological processes, MK itself as well as pharmaceuticals targeting MK and its signalling system are expected to be valuable for the treatment of numerous diseases. LINKED ARTICLESThis article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 Abbreviations ALK, anaplastic lymphoma kinase; Hes-1, hairy and enhancer of split-1; HIF, hypoxia-induced factor; LRP, low-density lipoprotein receptor-related protein; Mdka, Midkine-a; Mdkb, Midkine-b; MK, midkine; PTN, pleiotrophin; PTPζ, receptor protein tyrosine phosphatase Z1

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Section: Mk Signallingmentioning

confidence: 97%

Section: Mk Signallingmentioning

confidence: 97%

Section: Mk In Development and Reproductionmentioning

confidence: 99%

Section: Mk Signallingmentioning

confidence: 99%

See 2 more Smart Citations

Structure and function of midkine as the basis of its pharmacological effects

Muramatsu

2014

British J Pharmacology

106

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“…Based on these findings, we analysed whether the anabolic response of bone to mechanical loading is influenced by Mdk deficiency (Liedert et al ., ). Therefore, we used the in vivo ulna loading model that has been demonstrated to promote endosteal and periosteal cortical bone formation in mice (Lee et al ., ).…”

Section: Midkine In Bone Remodellingmentioning

confidence: 97%

The role of midkine in skeletal remodelling

Liedert

Schinke

Ignatius

et al. 2014

British J Pharmacology

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Bone tissue is subjected to continuous remodelling, replacing old or damaged bone throughout life. In bone remodelling, the coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts ensure the maintenance of bone mass and strength. In early life, the balance of these cellular activities is tightly regulated by various factors, including systemic hormones, the mechanical environment and locally released growth factors. Age-related changes in the activity of these factors in bone remodelling can result in diseases with low bone mass, such as osteoporosis. Osteoporosis is a systemic and age-related skeletal disease characterized by low bone mass and structural degeneration of bone tissue, predisposing the patient to an increased fracture risk. The growth factor midkine (Mdk) plays a key role in bone remodelling and it is expressed during bone formation and fracture repair. Using a mouse deficient in Mdk, our group have identified this protein as a negative regulator of bone formation and mechanically induced bone remodelling. Thus, specific Mdk antagonists might represent a therapeutic option for diseases characterized by low bone mass, such as osteoporosis. LINKED ARTICLESThis article is part of a themed section on Midkine. To view the other articles in this section visit http://dx

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Midkine Deficiency Increases the Anabolic Response of Cortical Bone to Mechanical Loading

Cited by 2 publications

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Structure and function of midkine as the basis of its pharmacological effects

Structure and function of midkine as the basis of its pharmacological effects

The role of midkine in skeletal remodelling

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