Mitochondrial b-oxidation of adipose-derived fatty acids by osteoblast fuels parathyroid hormone-induced bone formation
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ABSTRACT:
PROVIDER: PRJNA918406 | ENA |
REPOSITORIES: ENA
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Project description:The energetic costs of bone formation require osteoblasts to coordinate their activities with tissues, like adipose, that can supply fuel molecules. In the case of intermittent parathyroid hormone treatment (PTH), a strategy used to reduce fracture risk, bone formation is proceeded by a change in lipid homeostasis. To investigate the requirement for fatty acid oxidation by osteoblasts during PTH-induced bone formation, we subjected mice with osteoblast-specific deficiency of mitochondrial long-chain b-oxidation as well as mice with adipocyte-specific deficiency for the PTH receptor or adipose triglyceride lipase to an anabolic treatment regime. PTH increased b-oxidation by osteoblasts and the release of fatty acids from adipocytes, while the genetic mouse models were resistant to the hormone’s anabolic effect. Collectively, these data suggest that PTH’s anabolic actions requires coordinated signaling in bone as well as in adipose, wherein a lipolytic response liberates fatty acids that are oxidized by osteoblasts to fuel bone formation
2023-04-12 | GSE222173 | GEO
Project description:The energetic costs of bone formation require osteoblasts to coordinate their activities with tissues, like adipose, that can supply energy-dense macronutrients. In the case of intermittent parathyroid hormone (PTH) treatment, a strategy used to reduce fracture risk, bone formation is preceded by a change in systemic lipid homeostasis. To investigate the requirement for fatty acid oxidation by osteoblasts during PTH-induced bone formation, we subjected mice with osteoblast-specific deficiency of mitochondrial long-chain β-oxidation as well as mice with adipocyte-specific deficiency for the PTH receptor or adipose triglyceride lipase to an anabolic treatment regimen. PTH increased the release of fatty acids from adipocytes and β-oxidation by osteoblasts, while the genetic mouse models were resistant to the hormone's anabolic effect. Collectively, these data suggest that PTH's anabolic actions require coordinated signaling between bone and adipose, wherein a lipolytic response liberates fatty acids that are oxidized by osteoblasts to fuel bone formation.
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Project description:Parathyroid hormone exacerbates pulmonary hypertension through hypoxia-induced parathyroid hormone receptor upregulation.
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Project description:The effect of parathyroid hormone (PTH) treatment was tested on osteoblasts prepared from calvaria of C57BL/6J mice 7-10 days old. Osteoblasts were treated with either human parathyroid hormone (1-34), bovine (D-Trp12,Tyr34) parathyroid hormone (7-34) amide or vehicle control for 4 hr. Gene expression effects were evaluated by DNA microarray.
2022-07-28 | GSE181284 | GEO
Project description:The effect of parathyroid hormone (PTH) analog treatment was tested on osteoblasts prepared from calvaria of C57BL/6J mice 7-10 days old. Osteoblasts were treated for 4 hr with either human parathyroid hormone (1-34) (hPTH(1-34), bovine (D-Trp12,Tyr34)-PTH(7-34) amide (bPTH(7-34)), bPTH(3-34), hPTH(1-31), or hPTH(7-34). Gene expression effects were evaluated by DNA microarray.
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Project description:The aim of this study was to explore the involvement of long noncoding RNAs (lncRNAs) during intermittent parathyroid hormone (PTH) induced cementogenesis.
2022-07-06 | GSE207523 | GEO
Project description:Osteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although the mechanisms underlying this phenomenon are unclear. Here we identified a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a novel coupling factor that is involved in the PTH-mediated shift to the osteoblastic phase. SLPI was highly upregulated in osteoblasts by PTH, and genetic ablation of SLPI severely impaired PTH-induced bone formation. SLPI induction in osteoblasts enhanced osteoblast differentiation intracellularly and was also secreted extracellularly, attracting neighboring osteoclasts to suppress osteoclastic function. Intravital bone imaging revealed that the PTH-mediated association between osteoblasts and osteoclasts was disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI, a previously unrecognized bone-coupling factor, mediates the communication of osteoblasts with osteoclasts to promote PTH-induced bone formation.
2021-01-17 | GSE145462 | GEO
Project description:Daily injection of parathyroid hormone (PTH) is a clinically approved treatment for osteoporosis. It suppresses apoptosis of bone-forming osteoblasts although its exact anti-apoptotic mechanism(s) is incompletely understood. In this study, PTH treatment of cultured osteoblasts blocked the pro-apoptotic effects of serum withdrawal and nutrient deprivation; hydrogen peroxide induced oxidative stress, and UV irradiation. We hypothesized that PTH might suppress osteoblast apoptosis by enhancing DNA repair. Evidence is provided showing that post-confluent, non-proliferating osteoblasts treated with PTH exhibited a protein kinase A-mediated activation of two proteins that regulate DNA repair processes (proliferating cell nuclear antigen and forkhead box transcription factor 3a) as well as a suppression of the pro-apoptotic growth arrest and DNA damage protein 153. Additional proof of a connection between DNA damage and osteoblast apoptosis came from an unexpected finding whereby a majority of fixed PTH-treated osteoblasts scored weakly positive for Terminal Deoxynucleotidyl dUTP Nick-End Labeling (TUNEL), even though similar cultures were determined to be viable via a trypsin replating strategy. TUNEL identifies DNA excision repair, not just apoptotic DNA fragmentation, and the most likely explanation of these TUNEL results is that PTH's activation of DNA repair processes would permit nucleotide incorporation as a result of enhanced excision repair. This explanation was confirmed by an enhanced incorporation of bromodeoxyuridine in PTH-treated cells even though a majority of the cell population was determined to be non-replicating. An augmentation of DNA repair by PTH is an unreported finding, and provides an additional explanation for its anti-apoptotic mechanism(s).
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Project description:Primary hyperparathyroidism is a common endocrine disorder frequently affecting postmenopausal women. In this study we have investigated expression of the prolactin receptor (PRLr) in a panel of 37 sporadic parathyroid tumours, as well as functionality in vitro in cultured parathyroid tumour cells. High levels of the prolactin receptor gene (PRLR) transcripts were demonstrated in parathyroid tissues as compared to other reference tissues and breast cancer cells. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours PRLr immunoreactivity was observed in cytoplasm in all cases and in addition in the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim PRLr was expressed in cytoplasm and granulae. In in vitro studies of short-term cultured human parathyroid tumour cells prolactin stimulation was associated with transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signaling pathways as documented by gene expression profiling. Moreover, PRLR gene expression in parathyroid tumors was significantly inversely correlated with plasma total Ca2+ levels. In conclusion, the prolactin receptor was found highly abundant in human parathyroid gland, parathyroid tumours, correlated with patient Ca2+ levels and functionally responsive to physiological levels of prolactin. These findings suggest a role for the prolactin receptor in human parathyroid adenomas.
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