npy and bone

PURPOSE OF REVIEW: Opioids have been shown to be associated with an increased risk of fracture. The purpose of this paper is to review recent research into the effects of opioids on bone formation and bone healing in animal models and in human studies. RECENT FINDINGS: Most opioids, such as morphine and fentanyl, negatively affected bone remodeling and bone healing in animal models. Conversely, remifentanil has been recently shown to promote in vitro osteoblast differentiation and to inhibit differentiation and maturation of osteoclasts, therefore reducing bone resorption...

Postoperative exercise has been found able to accelerate bone-tendon (B-T) healing. In this study, we systematically compared tendon-to-bone healing in mice subjected to postoperative treadmill exercise and free cage recovery in a murine rotator cuff repair model. Specifically, C57BL/6 mice underwent unilateral supraspinatus tendon (SST) detachment and repair were randomly allocated into treadmill group and control group. Treadmill group received daily treadmill running initiated from postoperative day 7 while the control group was allowed free cage activity...

OBJECTIVE: Neuropeptide Y (NPY) has been shown to have a prominent role in the control of bone formation through the regulation of osteoblast activity. We aimed to investigate the role of hypothalamus-derived NPY in bone metabolism. METHODS: Accordingly, adeno-associated virus (AAV)-mediated RNA interference (RNAi) was utilized to downregulate NPY gene expression in rats fed regular chow (RC) or a high-fat diet (HF). The serum concentrations of glucose, insulin, corticosterone, osteocalcin, insulin-like growth factor (IGF-1), triglycerides (TC), and cholesterol (TG) and fat mass and bone mineral density (BMD) were measured to assess the effect of NPY knockdown on basal and obesity-induced BMD...

In Traditional Chinese Medicine (TCM), the 'tonifying kidney and benefiting marrow' (TKBM) method is based on the theory that kidney controls bones, while marrow moistens bones. There have been aboundant theoretical studies on kidney controlling bones since Huangdi's Internal Classics. However, there are too few ones about the marrow moistening the bones. Researchers generally use the tonifying kidney method instead of the TKBM method, which causes lack of a unified standard and theoretical basis in evaluating the TKBM method...

BACKGROUND/OBJECTIVES: Maintaining energy balance is important to ensure a healthy organism. However, energy partitioning, coordinating the distribution of sufficient energy to different organs and tissues is equally important, but the control of this process is largely unknown. In obesity, an increase in fat mass necessitates the production of additional bone mass to cope with the increase in bodyweight and processes need to be in place to communicate this new weight bearing demand. Here, we investigate the interaction between leptin and NPY, two factors critically involved in the regulation of both energy metabolism and bone mass, in this process...

Differentiation, self-renewal and quiescence of Hematopoietic stem cells (HSCs) is tightly regulated in order to protect the HSCs from the strain of constant cell division and depletion of the stem cell pool. The neurotransmitter Neuropeptide Y (NPY) is released from sympathetic nerves in the bone marrow and has been shown to indirectly affect HSC function through effects on bone marrow (BM) multipotent Mesenchymal Stromal Cells (MSCs), osteoblasts (OBs) and macrophages. Although the absence of NPY has been shown to be accompanied by severe BM impairment and delayed engraftment of HSCs, the direct effects of NPY on HSCs have never been assessed...

Neuropeptide Y (NPY) is known to regulate bone homeostasis; however, its functional role as a risk factor during osteoarthritis (OA) remains elusive. In this study, we aim to investigate the direct effect of NPY on degradation of cartilage and progression of OA and explore the molecular events involved. NPY was overexpressed in human OA cartilage accompanied with increased expression of NPY1 receptor (NPY1R) and NPY2 receptor (NPY2R). Stressors such as cold exposure resulted in the peripheral release of NPY from sympathetic nerves, which in turn promoted upregulation of NPY and NPY2R in articular cartilage in vivo...

Energy metabolism and bone homeostasis share several neuronal regulatory pathways. Within the ventral hypothalamus (VHT), the orexigenic neurons co-express Agouti-related peptide (AgRP) and neuropeptide Y (NPY) and the anorexigenic neurons co-express, α-melanocyte stimulating hormone derived from proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART). These neurons regulate both processes, yet their relative contribution is unknown. Previously, using genetically targeted AP1 alterations as a tool, we showed in adult mice that AgRP or POMC neurons are capable of inducing whole body energy catabolism and bone accrual, with different effects on bone resorption...

Genetic and pharmacological functional studies have provided evidence that the lack of Neuropeptide Y-Y1  receptor (Y1 R) signaling pathway induces a high bone mass phenotype in mice. However, clinical observations have shown that drug or genetic mediated improvement of bone mass might be associated to alterations to bone extracellular matrix (ECM) properties, leading to bone fragility. Hence, in this study we propose to characterize the physical, chemical and biomechanical properties of mature bone ECM of germline NPY-Y1 R knockout (Y1 R-/- ) mice, and compare to their wild-type (WT) littermates...

A plethora of evidence has suggested that gut microbiota is involved in the occurrence and development of postmenopausal osteoporosis (PMO). It has been suggested that neuropeptide Y (NPY) modulates the bone metabolism through Y1 receptor (Y1R), and might be associated with gut microbiota. The present study aims to evaluate the anti-osteoporotic effects of Y1R antagonist and to investigate the potential mechanism by which Y1R antagonist regulates gut microbiota. In this study, eighteen female rats were randomly divided into three groups: the sham surgery (SHAM) group, the ovariectomized (OVX) group, and OVX+BIBO3304 group...

OBJECTIVES: Postmenopausal osteoporosis (PMO) is a metabolic skeletal disorder with impaired bone density and bone quality in postmenopausal women. The aim of the present study was to investigate the correlation between neuropeptides, bone microstructure and pain threshold in ovariectomized (OVX) rats. METHODS: Female rats were randomly divided into the ovariectomized (OVX) group and the sham surgery (SHAM) group. Bone microstructure and immunocytochemistry for substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) in tibial and DRG were performed...

Neuropeptide Y (NPY) producing neurons in the arcuate nucleus (Arc) of the hypothalamus are essential to the regulation of food intake and energy homeostasis. Whilst they have classically been thought to co-express agouti-related peptide (AgRP), it is now clear that there is a sub-population of NPY neurons in the Arc that do not. Here, we show that a subset of AgRP-negative, NPY-positive neurons in the Arc also express neurotensin (NTS) and we use an NTS-Cre line to investigate the function of this sub-population of NPY neurons...

The bone marrow (BM) hematopoietic niche is the microenvironment where in the adult hematopoietic stem and progenitor cells (HSPCs) are maintained and regulated. This regulation is tightly controlled through direct cell-cell interactions with mesenchymal stromal stem (MSCs) and reticular cells, adipocytes, osteoblasts and endothelial cells, through binding to extracellular matrix molecules and through signaling by cytokines and hematopoietic growth factors. These interactions provide a healthy environment and secure the maintenance of the HSPC pool, their proliferation, differentiation and migration...

Bone homeostasis displays a circadian rhythm with increased resorption during the night time as compared to day time, a difference that seems-at least partly-to be caused by food intake during the day. Thus, ingestion of a meal results in a decrease in bone resorption, but people suffering from short bowel syndrome lack this response. Gut hormones, released in response to a meal, contribute to this link between the gut and bone metabolism. The responsible hormones appear to include glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), known as incretin hormones due to their role in regulating glucose homeostasis by enhancing insulin release in response to food intake...

The RANKL pathway is known to be an important aspect of the pathogenesis of estrogen-deficiency induced bone loss. RANK deletion specifically in NPY neurons has been shown to enhance the ability of the skeleton to match increases in body weight caused by high fat diet feeding, likely via the modulation of NPY levels. Here, we use ovariectomy in female mice to show that RANK deletion in NPY neurons attenuates bone loss caused by long-term estrogen deficiency, particularly in the vertebral compartment. Ovariectomy led to a reduction in NPY expression levels in the arcuate nucleus of NPYcre/+ ;RANKlox/lox mice compared to NPYcre/+ ;RANKlox/+ controls...

Neuropeptide Y (NPY) is involved in multiple processes such as behavior, energy and bone metabolism. Previous studies have relied on global NPY depletion to examine its effects on bone. However, this approach is unable to distinguish the central or local source of NPY influencing bone. Our aim was to identify which cells within the skeleton express Npy and establish a model that will enable us to differentiate effects of NPY derived from different cell types. We have generated the NPY floxed (NPYflox ) mice using CRISPR technology...

Chemotherapy-induced bone marrow damage is accompanied by acute nerve injury in the bone marrow (BM), resulting in sensory and autonomic neuropathy. Cisplatin, a popular chemotherapy drugs, induces the impairment of hematopoietic stem cells (HSCs) and bone marrow regeneration, leading to chronic bone marrow abnormalities. Previously, we reported the protective roles of neuropeptide Y (NPY) against cisplatin-induced bone marrow impairment. In this study, we identified novel peptides, generated from full-length NPY that rescued cisplatin-induced sensory neuropathy and HSC suppression by regulating cell survival in the BM microenvironment...

The function of melatonin (MLT) in promoting fracture healing has been demonstrated in previous studies. However, the molecular mechanism underlying therapeutic effects of MLT is not entirely clear. In this study, mesenchymal stem cells (MSCs) were isolated from rat bone marrow and identified by flow cytometry. We found that MLT treatment upregulated the neuropeptide Y (NPY) and NPY receptor Y1 (NPY1R) expression, and promoted the proliferation and migration of MSCs, which was suppressed by BIBP3226, an inhibitor of NPY1R...

OBJECTIVE: To investigate the effects of neuropeptide Y (NPY) Y1 receptor antagonist PD160170 in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and accelerating healing of femoral defect in rats. METHODS: The third generation of rat BMSCs were treated with PBS (control) or 10-6 , 10-7 , or 10-8 mol/L NPY Y1 receptor antagonist PD160170. After 7 and 14 days of treatment, the cells were examined for osteogenic differentiation with alkaline phosphatase (ALP) and alizarin red staining...

The present antiepileptic drugs pose several problems in the management of seizures owing to their meager neuroprotective potential, adverse effects on bone, detrimental effects on cognitive function, chronic toxicity, drug interactions, side effects including aggression, agitation, and irritability and sometimes exacerbation of seizures. We followed up progressive preclinical investigation in mice against pilocarpine (PILO)-induced status epilepticus (SE) and temporal lobe epilepsy (TLE). To determine the response of raloxifene (RF) (4 and 8 mg/kg), fluoxetine (FT) (14 and 22 mg/kg), bromocriptine (BC) (6 and 10 mg/kg), and their low-dose combinations, oral treatment was scheduled for 28 days followed by PILO (300 mg/kg, i...