Cortical bone is an extraneuronal site of norepinephrine uptake in adult mice
| Autor: | Yuantee Zhu, Florent Elefteriou, Yun Ma |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Aging Sympathetic nervous system medicine.medical_specialty lcsh:Diseases of the musculoskeletal system Endocrinology Diabetes and Metabolism Uptake Transporter Article Imaging Norepinephrine uptake Bone remodeling Norepinephrine 03 medical and health sciences Tracing Internal medicine medicine Orthopedics and Sports Medicine biology Tyrosine hydroxylase Chemistry Osteocyte 030104 developmental biology medicine.anatomical_structure Endocrinology Norepinephrine transporter biology.protein Cortical bone Sympathetic nerves lcsh:RC925-935 medicine.drug |
| Zdroj: | Bone Reports, Vol 9, Iss, Pp 188-198 (2018) Bone Reports |
| ISSN: | 2352-1872 |
| Popis: | The sympathetic nervous system is a major efferent pathway through which the central nervous system controls the function of peripheral organs. Genetic and pharmacologic evidence in mice indicated that stimulation of the β2 adrenergic receptor (β2AR) in osteoblasts promotes bone loss, leading to the paradigm that high sympathetic nervous activity is deleterious to bone mass. However, considerably less data exist to understand the putative impact of endogenous norepinephrine (NE), released by sympathetic nerves, on bone homeostasis. In this study, we investigated the in vivo expression and activity of the norepinephrine transporter (NET), a membrane pump known to actively uptake NE from the extracellular space in presynaptic neurons. Consistent with previously published in vitro data showing NET uptake activity in differentiated osteoblasts, we were able to detect active NET-specific NE uptake in the mouse cortical bone compartment in vivo. This uptake was the highest in young mice and accordingly with an age-related reduction in NET uptake, NE bone content increased whereas Net RNA and protein expression decreased with age. Histologically, NET expression in adult mouse bones was detected in osteocytes via immunofluorescence. Lastly, taking advantage of tissue-specific fluorescent reporter mice, we used CLARITY imaging and light sheet microscopy to visualize the 3D distribution of sympathetic fibers in whole mount preparations of bone tissues. These analyses allowed us to detect tyrosine hydroxylase (TH)-positive sympathetic nerve fibers penetrating the cortical bone, where NET+ osteocytes reside. Together, these in vitro results support the existence of an age-dependent extraneuronal and osteocytic function of NET with potential to buffer the bone catabolic action of endogenous NE released by sympathetic nerves in vivo. Highlights • The NE transporter (NET) is expressed in adult mouse cortical osteocytes. • The mouse cortical bone compartment is a site of in vivo NE uptake. • Osteocytes express NE catabolic but not NE synthesis enzymes • NET expression and NE uptake by NET in cortical bone decrease with age. • TH-positive nerve fibers penetrate cortical bone where NET+ osteocytes reside. |
| Databáze: | OpenAIRE |
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