Neuromodulation of bone: Role of different peptides and their interactions (Review)

Wang, Xiaoyu; Xu, Jia; Kang, Qinglin

doi:10.3892/mmr.2020.11670

Cited by 11 publications

(16 citation statements)

References 139 publications

(300 reference statements)

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“…Neuropeptides are involved in the regulation of bone metabolism, influencing the activity of bone cells, including osteoblasts, osteoclasts, and osteocytes [ 1 , 2 , 34 , 35 ]. Nevertheless, the role in bone of opioids, a specific class of neuropeptides, is still partially unclear and the complexity of their signalling pathway further complicates the scenario.…”

Section: Discussionmentioning

confidence: 99%

“…Recent research has shown that neuropeptides affect the functions of bone cells playing an essential role in the metabolism of the skeletal tissues [ 1 , 2 ]. Pre-proenkephalin 1 ( Penk1 ) is a gene encoding a pro-neuropeptide that is proteolytically processed to generate the following enkephalins: [Met]-enkephalin, [Met]-enkephalin extended sequence, and [Leu]-enkephalin, all belonging to the family of opioid peptides that are endogenous ligands for opioid receptors having potent analgesic properties [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Pre-proenkephalin 1 is Downregulated Under Unloading and is Involved in Osteoblast Biology

Puri,

Dannenberg,

Ucci

et al. 2024

Calcif Tissue Int

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Pre-proenkephalin 1 (Penk1) is a pro-neuropeptide that belongs to the typical opioid peptide’s family, having analgesic properties. We previously found Penk1 to be the most downregulated gene in a whole gene profiling analysis performed in osteoblasts subjected to microgravity as a model of mechanical unloading. In this work, Penk1 downregulation was confirmed in the bones of two in vivo models of mechanical unloading: tail-suspended and botulinum toxin A (botox)-injected mice. Consistently, in the sera from healthy volunteers subjected to bed rest, we observed an inverse correlation between PENK1 and bed rest duration. These results prompted us to investigate a role for this factor in bone. Penk1 was highly expressed in mouse bone, but its global deletion failed to impact bone metabolism in vivo. Indeed, Penk1 knock out (Penk1−/−) mice did not show an overt bone phenotype compared to the WT littermates. Conversely, in vitro Penk1 gene expression progressively increased during osteoblast differentiation and its transient silencing in mature osteoblasts by siRNAs upregulated the transcription of the Sost1 gene encoding sclerostin, and decreased Wnt3a and Col1a1 mRNAs, suggesting an altered osteoblast activity due to an impairment of the Wnt pathway. In line with this, osteoblasts treated with the Penk1 encoded peptide, Met-enkephalin, showed an increase of Osx and Col1a1 mRNAs and enhanced nodule mineralization. Interestingly, primary osteoblasts isolated from Penk1−/− mice showed lower metabolic activity, ALP activity, and nodule mineralization, as well as a lower number of CFU-F compared to osteoblasts isolated from WT mice, suggesting that, unlike the transient inhibition, the chronic Penk1 deletion affects both osteoblast differentiation and activity. Taken together, these results highlight a role for Penk1 in the regulation of the response of the bone to mechanical unloading, potentially acting on osteoblast differentiation and activity in a cell-autonomous manner.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pre-proenkephalin 1 is Downregulated Under Unloading and is Involved in Osteoblast Biology

Puri,

Dannenberg,

Ucci

et al. 2024

Calcif Tissue Int

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“…49 Furthermore, sensory nerve fibers are more densely innervated in the epiphysis compared to the metaphysis, and are mainly restricted to vascularized CD31 + Haversian canals. 1,50 Sensory nerves can be classified by their receptors and channels, such as toll-like receptors, tyrosine kinase receptors, transient receptor potential ion channels, and mechanosensitive Piezo channels. 44,51 These receptors and channels initiate intracellular signaling and the release of neuropeptides.…”

Section: Sensory Afferents Mediate Interoceptive Signals To Facilitat...mentioning

confidence: 99%

Interoceptive regulation of skeletal tissue homeostasis and repair

Xiao,

Han,

Wang

et al. 2023

Bone Res

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Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue, a process known as skeletal interoception, which is crucial for maintaining bone homeostasis. The hypothalamus, located in the central nervous system (CNS), plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system, neuropeptide release, and neuroendocrine mechanisms. These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts (OBs), the activation of osteoclasts (OCs), and the functional activities of bone cells. Sensory nerves extensively innervate skeletal tissues, facilitating the transmission of interoceptive signals to the CNS. This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions. The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.

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“…Neuropeptides impact a large and diverse array of physiological processes (Insel, 2010; Mills et al, 2020; Neumann & Landgraf, 2012; Steinhoff et al, 2014; Wang et al, 2021; Xu et al, 2020). Functional elucidation is not trivial notably due to neuropeptide co‐transmission capabilities (Nusbaum et al, 2017) and pleiotropic nature (Souza‐Moreira et al, 2011).…”

Section: Functional Studiesmentioning

confidence: 99%

Recent advances in mass spectrometry analysis of neuropeptides

Phetsanthad

et al. 2021

Mass Spectrometry Reviews

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Due to their involvement in numerous biochemical pathways, neuropeptides have been the focus of many recent research studies. Unfortunately, classic analytical methods, such as western blots and enzyme‐linked immunosorbent assays, are extremely limited in terms of global investigations, leading researchers to search for more advanced techniques capable of probing the entire neuropeptidome of an organism. With recent technological advances, mass spectrometry (MS) has provided methodology to gain global knowledge of a neuropeptidome on a spatial, temporal, and quantitative level. This review will cover key considerations for the analysis of neuropeptides by MS, including sample preparation strategies, instrumental advances for identification, structural characterization, and imaging; insightful functional studies; and newly developed absolute and relative quantitation strategies. While many discoveries have been made with MS, the methodology is still in its infancy. Many of the current challenges and areas that need development will also be highlighted in this review.

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Neuromodulation of bone: Role of different peptides and their interactions (Review)

Cited by 11 publications

References 139 publications

Pre-proenkephalin 1 is Downregulated Under Unloading and is Involved in Osteoblast Biology

Pre-proenkephalin 1 is Downregulated Under Unloading and is Involved in Osteoblast Biology

Interoceptive regulation of skeletal tissue homeostasis and repair

Recent advances in mass spectrometry analysis of neuropeptides

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