805 Familial Lipoprotein Lipase Deficiency

Penava, S; Bajraktarevic, Adnan; Selimović, Amina; Abduzaimovic, D; Musabegovic, J; Frankic, Teodora; Čaušević, Adlija; Korać, Selma; Djulepa, Aida Djurdjevic; Boloban, Hamdo

doi:10.1203/00006450-201011001-00805

Cited by 2 publications

(2 citation statements)

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“…Since CNP also increases intracellular cGMP concentrations in primary osteoblasts, it is surprising that these mice do not have increased bone formation rates and show decreased trabecular bone volumes in the femurs of 8 week-old females (data on transgenic males were not reported) (Kondo et al 2015). Whether CNP stimulates or inhibits osteoblast proliferation is controversial (Lenz et al 2010; Hagiwara et al 1996). The reason for these inconsistencies is unclear, but cGMP pools generated by soluble versus receptor GCs may be compartmentalized and differentially activate PKG1 and 2 in different cell types.…”

Section: Discussionmentioning

confidence: 99%

cGMP-dependent protein kinase-2 regulates bone mass and prevents diabetic bone loss

Ramdani

Schall

Kalyanaraman

et al. 2018

Journal of Endocrinology

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NO/cGMP signaling is important for bone remodeling in response to mechanical and hormonal stimuli, but the downstream mediator(s) regulating skeletal homeostasis are incompletely defined. We generated transgenic mice expressing a partly-activated, mutant cGMP-dependent protein kinase type 2 (PKG2) under control of the osteoblast-specific Col1a1 promoter to characterize the role of PKG2 in post-natal bone formation. Primary osteoblasts from these mice showed a two- to three-fold increase in basal and total PKG2 activity; they proliferated faster and were resistant to apoptosis compared to cells from WT mice. Male Col1a1- transgenic mice had increased osteoblast numbers, bone formation rates and Wnt/β-catenin-related gene expression in bone and a higher trabecular bone mass compared to their WT littermates. Streptozotocin-induced type 1 diabetes suppressed bone formation and caused rapid bone loss in WT mice, but male transgenic mice were protected from these effects. Surprisingly, we found no significant difference in bone micro-architecture or Wnt/β-catenin-related gene expression between female WT and transgenic mice; female mice of both genotypes showed higher systemic and osteoblastic NO/cGMP generation compared to their male counterparts, and a higher level of endogenous PKG2 activity may be responsible for masking effects of the PKG2 transgene in females. Our data support sexual dimorphism in Wnt/β-catenin signaling and PKG2 regulation of this crucial pathway in bone homeostasis. This work establishes PKG2 as a key regulator of osteoblast proliferation and post-natal bone formation.

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Section: Discussionmentioning

confidence: 99%

cGMP-dependent protein kinase-2 regulates bone mass and prevents diabetic bone loss

Ramdani

Schall

Kalyanaraman

et al. 2018

Journal of Endocrinology

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“…Generally, CNP is considered an endothelium-derived peptide and positively regulates bone formation. Lenz et al cultured CRL-11372 human osteoblast cells with different concentrations of CNP (10, 100 pM, 1, and 10 nM) for 7 days and revealed that the pro-osteoblastic effect of CNP also showed a dose-specific response; 10 nM CNP exerted the highest acceleration of osteoblast proliferation (~30%) 41 . To the best of our knowledge, elevated FGF-23, together with decreased CNP, is often observed in CKD.…”

Section: Discussionmentioning

confidence: 99%

C-type natriuretic peptide attenuates renal osteodystrophy through inhibition of FGF-23/MAPK signaling

Zhang

Chen

et al. 2019

Exp Mol Med

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Renal osteodystrophy (ROD) occurs as early as chronic kidney disease (CKD) stage 2 and seems ubiquitous in almost all pediatric patients with CKD stage 5. Fibroblast growth factor (FGF)-23, a bone-derived endocrine regulator of phosphate homeostasis, is overexpressed in CKD and disturbs osteoblast differentiation and matrix mineralization. In contrast, C-type natriuretic peptide (CNP) acts as a potent positive regulator of bone growth. In the present study, we infused CNP into uremic rats and observed whether CNP could attenuate ROD through the inhibition of FGF-23 cascades. In uremic rats, CNP administration significantly alleviated renal dysfunction, calcium phosphate metabolic disorders, hypovitaminosis D, secondary hyperparathyroidism, the decrease in bone turnover markers and retarded bone pathological progression. More importantly, within FGF-23/mitogen-activated protein kinase (MAPK) signaling, the fibroblast growth factor receptor-1, Klotho and alternative (STAT-1/phospho-STAT-1) elements were upregulated by CNP, whereas FGF-23, RAF-1/phospho-RAF-1, and downstream (ERK/phospho-ERK and P38/phospho-P38) elements were paradoxically underexpressed in bone tissue. Therefore, CNP exerts a therapeutic effect on ROD through inhibition of FGF-23/MAPK signaling at the RAF-1 level.

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805 Familial Lipoprotein Lipase Deficiency

Cited by 2 publications

References 0 publications

cGMP-dependent protein kinase-2 regulates bone mass and prevents diabetic bone loss

cGMP-dependent protein kinase-2 regulates bone mass and prevents diabetic bone loss

C-type natriuretic peptide attenuates renal osteodystrophy through inhibition of FGF-23/MAPK signaling

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