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Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells.

ABSTRACT: Orexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecholamine synthesis, including tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanie decarboxylase (Ddc) and dopamine β-hydroxylase (Dbh), in a concentration-dependent manner. On the other hand, treatment with BMP-4 suppressed the expression of Th and Ddc but enhanced that of Dbh with or without co-treatment with orexin A. Of note, orexin A augmented BMP-receptor signaling detected by the phosphorylation of Smad1/5/9 through the suppression of inhibitory Smad6/7 and the upregulation of BMP type-II receptor (BMPRII). Furthermore, treatment with BMP-4 upregulated the mRNA levels of OX1R in PC12 cells. Collectively, the results indicate that orexin and BMP-4 suppress adrenomedullary catecholamine synthesis by mutually upregulating the pathway of each other in adrenomedullary cells.

SUBMITTER: Soejima Y

PROVIDER: S-EPMC10855520 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells.

Soejima Yoshiaki Y Iwata Nahoko N Yamamoto Koichiro K Suyama Atsuhito A Nakano Yasuhiro Y Otsuka Fumio F

International journal of molecular sciences 20240127 3

Orexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecho ...[more]

PMID: 38338864

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Project description:Osteochondral tissue-engineered grafts are proposed to hold greater potential to repair/regenerate damaged cartilage through enhanced biochemical and mechanical interactions with underlying subchondral bone as compared to simple engineered cartilage. Additionally, biomechanical stimulation of articular chondrocytes (ACs) or osteoblasts (OBs) was shown to induce greater morphogenesis of the engineered tissues composed of these cells. In this report, to define the advantages of biomechanical stimulation to osteochondral grafts for tissue engineering, we examined whether (1) ACs and OBs in three-dimensional (3D) osteochondral constructs support functional development of each other at the molecular level, and (2) biomechanical stimulation of osteochondral constructs further promotes the regenerative potential of such grafts. Various configurations of cell/scaffold assemblies, including chondral, osseous, and osteochondral constructs, were engineered with mechano-responsive electrospun poly(ɛ-caprolactone) scaffolds. These constructs were subjected to either static or dynamic (10% cyclic compressive strain at 1 Hz for 3 h/day) culture conditions for 2 weeks. The expression of bone morphogenetic proteins (BMPs) was examined to assess the regenerative potential of each treatment on the cells. Biomechanical stimulation augmented a marked upregulation of Bmp2, Bmp6, and Bmp7 as well as downregulation of BMP antagonist, Bmp3, in a time-specific manner in the ACs and OBs of 3D osteochondral constructs. More importantly, the presence of biomechanically stimulated OBs was especially crucial for the induction of Bmp6 in ACs, a BMP required for chondrocytic growth and differentiation. Biomechanical stimulation led to enhanced tissue morphogenesis possibly through this BMP regulation, evident by the improved effective compressive modulus of the osteochondral constructs (710 kPa of dynamic culture vs. 280 kPa of static culture). Similar BMP regulation was observed in the femoral cartilages of the rats subjected to gentle exercise, demonstrating the physiological relevance of in vitro biomechanical stimulation of osteochondral constructs. Overall, our findings show that biomechanical stimulation may be critical for cross signaling between ACs and OBs to support chondrocytic growth in 3D osteochondral tissues.

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Dataset Information

Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells.

Publications

Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells.

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