Different skeletal regional response to continuous brain infusion of leptin in the rat

Guidobono, F.; Pagani, F.; Sibilia, V.; Netti, C.; Lattuada, N.; Rapetti, D.; Mrak, Emanuela; Villa, Isabella; Cavani, Francesco; Bertoni, Laura; Palumbo, Carla; Ferretti, Marzia; Marotti, Gastone; Rubinacci, Alessandro

doi:10.1016/j.peptides.2005.10.014

Cited by 23 publications

(15 citation statements)

References 33 publications

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“…This observation is in line with previous data showing regional and structural differences in bone after the central infusion of leptin, which is known to stimulate the SNS [Takeda et al, 2002]. In growing rats central leptin was seen to reduce trabecular bone in femura and tibiae but not in vertebrae, moreover to increase cortical bone in tibiae [Guidobono et al, 2006]. These observations support the view that the SNS might be more involved in a modulatory role in controlling bone mass as a function of the mechanical environment rather than affecting the trabecular compartment which is more involved in the organism metabolic needs.…”

Section: Discussionsupporting

confidence: 92%

Sympathectomy alters bone architecture in adult growing rats

Pagani

Sibilia

Cavani

et al. 2008

J of Cellular Biochemistry

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Sympathetic nervous system (SNS) fibres and alpha- and beta-receptors are present in bone, indicating that the SNS may participate in bone metabolism. The importance of these observations is controversial because stimulation or inhibition of the SNS has had various effects upon both anabolic and catabolic activity in this tissue. In this study we evaluated the effects of pharmacological sympathectomy, using chronic treatment of maturing male rats with 40 mg of guanethidine/kg i.p., upon various parameters in bone. Double labelling with tetracycline injection was also performed 20 and 2 days before sacrifice. Bone mass, mineral content, density and histomorphometric characteristics in different skeletal regions were determined. Bone metabolic markers included urinary deoxypyridinoline and serum osteocalcin measurements. Guanethidine significantly reduced the accretion of lumbar vertebral bone and of mineral content and density, compared to controls. Femoral bone mineral content and density were also significantly reduced, compared to controls. Histomorphometric analyses indicated these effects were related to a reduction of cortical bone and mineral apposition rate at femoral diaphysials level. Both markers of bone metabolism were reduced in controls as they approached maturity. Guanethidine significantly decreased serum osteocalcin compared to controls, while urinary deoxypyridinoline was unchanged. These data indicate that guanethidine-induced sympathectomy caused a negative balance of bone metabolism, leading to decreased mass by regulating deposition rather than resorption during modeling and remodeling of bone.

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Section: Discussionsupporting

confidence: 92%

Sympathectomy alters bone architecture in adult growing rats

Pagani

Sibilia

Cavani

et al. 2008

J of Cellular Biochemistry

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“…GTG-lesionned mice were however still responsive to leptin's anorexigenic effect, in agreement with the integrity of arcuate neurons in this model, indicating that leptin-induced bone loss was not due to starvation. Leptin's use of a central relay for regulating bone mass was then demonstrated in rats and sheep by similar means [6,8,9].…”

Section: The Central Nervous System Restrains Bone Formationmentioning

confidence: 97%

Regulation of bone remodeling by the central and peripheral nervous system

Elefteriou

2008

Archives of Biochemistry and Biophysics

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The homeostatic nature of bone remodeling has become a notion further supported lately by the demonstration that neuropeptides and their receptors regulate osteoblast and osteoclast function in vivo. Following initial studies reporting the presence of nerves and nerve-derived products within the bone micro-environment and the expression of receptors for these neuropeptides in bone cells, new experimental and mechanistic evidence based on in vivo murine genetic and pharmacologic models recently demonstrated that inputs from the central and peripheral nervous system feed into the already complex regulatory machinery controlling bone remodeling. The function of a number of "osteo-neuromediators" has been characterized, including norepinephrine and the beta 2-adrenergic receptor, Neuropeptide Y and the Y1 and Y2 receptors, endocannabinoids and the CB1 and CB2 receptors, as well as dopamine, serotonin and their receptors and transporters, Calcitonin gene-related peptide, and neuronal NOS. This new body of evidence suggests that neurons in the central nervous system integrate clues from the internal and external milieux, such as energy homeostasis, glycemia or reproductive signals, with the regulation of bone remodeling. The next major tasks in this new area of bone biology will be to understand, at the molecular level, the mechanisms by which common central neural systems regulate and integrate these major physiological functions, the relative importance of the central and peripheral actions of neuropeptides present in both compartments and their relationship, and how bone cells signal back to central centers, because the definition of a homeostatic function implies the existence of feedback signals. Together, these findings shed a new light on the complexity of the mechanisms regulating bone remodeling and uncovered new potential therapeutic strategies for the design of bone anabolic treatments. This review summarizes the latest advances in this area, focusing on investigations based on in vivo animal studies. KeywordsBone; osteoblast; osteoclast; neuron; sympathetic nervous system; hypothalamus; leptin; neuropeptide; adrenergic receptor; neuropeptide Y; endocannabinoid The central nervous system restrains bone formationIt is the association between body weight and bone density as well as the association between loss of gonadal function and osteoporosis that initially pointed to the putative existence of a common factor regulating body weight, reproduction and bone mass. Based on the knowledge that the adipocyte-derived hormone leptin regulates major physiological functions, including body weight and reproduction, via the hypothalamus and its receptor ObRb, it was

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“…In contrast, lesioning ventromedical hypothalamic nuclei neurons in wild type animals resulted in a high bone mass/high bone turnover phenotype similar to that observe in the ob/ob mice. Infusion of leptin failed to normalize the bone phenotype in either lesioned wild type mice or the ob/ob mice (Guidobono et al, 2006). Taken together, these data suggested that the ventromedical hypothalamic nucleus neurons are required for leptin-dependent central regulation of bone remodeling.…”

Section: Central Control Of Bone Remodelingmentioning

confidence: 80%