Correlation of neuropeptides substance P and neuropeptide Y and their receptors with fracture healing in rats

2020 ◽  
Vol 10 (2) ◽  
pp. 240-250
Author(s):  
Zhenlv Zou ◽  
Gang Mei ◽  
Liying Tang ◽  
Yafei Xu ◽  
Jun Liu ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Substance P ◽  
Bone Formation ◽  
Neuropeptide Y ◽  
Fracture Healing ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Callus Formation ◽  
Healing Process ◽  
Expression Levels

Bone fracture healing is a complex process involving a cascade of cellular and molecular events that are orchestrated by a variety of factors, including neuropeptides and their receptors. However, the roles of neuropeptides and their receptors in the fracture healing process are controversial. We monitored the expression and distribution of the neuropeptides, substance P (SP) and neuropeptide Y (NPY) and their receptors, neurokinin 1 receptor (NK1) and neuropeptide Y1 receptor (NPY1R), in rats undergoing fracture healing. Total RNA was extracted using Fe3O4 and was retrieved into DNA using the MagBeads Total RNA Extraction Kit. The expression levels of SP, NK1, and NPY at each time point in the healing bone tissue were found to be higher than the levels in normal bone tissue. Their location and expression levels correlated with the healing process. In the callus formation stage, the expression levels of SP, NK1, and NPY were found to be increased in the matrix of the cartilage, in chondrocytes, and in the subperiosteal region. At the bone remodeling stage, they were located in the periosteum, new bone tissue, and perivascular regions, and their expression levels gradually reduced. Therefore, we conclude that SP was involved in callus formation and bone resorption at different physiological concentrations. At some concentrations, SP positively regulated new bone formation via NK1. At other concentrations, the SP-NK1 interaction promoted bone resorption. Very low expression levels of NPY1R were observed at the early healing stage, but they increased at the middle stage and then decreased at the late stage. This indicated that NPY was involved in bone formation through NPY1R-unrelated mechanisms. NPY1R was more involved at the later stage of bone remodeling, according to its expression levels. NPY1R contributed to callus formation and remodeling.

scholarly journals Analysis of osteoblast, osteoclast levels and radiographic patterns in the healing process of bone fractures (preliminary research)

2021 ◽  
Vol 5 (3) ◽  
pp. 106
Author(s):  
Norlaila Sarifah ◽  
Lusi Epsilawati ◽  
Azhari Azhari ◽  
Mieke Hermiawati Satari ◽  
Bambang Pontjo Priosoeryanto ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Fracture Healing ◽  
Bone Fracture ◽  
Bone Fractures ◽  
Callus Formation ◽  
Healing Process ◽  
Lateral Position ◽  
Original Structure ◽  
Male Wistar Rats

Objectives: The healing process of a bone fracture goes through many phases. The hard callus phase was critical where the original structure was conducted. The hard callus growth depends on osteoblasts and osteoclasts active, and this condition can be analyzed on the radiograph. This study aimed to examine the analysis of bone fracture healing between osteoblasts and osteoclast numbers and radiographic patterns. Materials and Methods: The study used 12 male Wistar rats with an incomplete fracture in the right femur made by a dental tapered bur with 0.3 mm in length and 0.2 mm in depth. Digital radiographic examinations were carried out on days 0, 5, 10, 17, and 25 after fracturing in a lateral position. Furthermore, a radiographic analysis was performed using Image-J to obtain changes in the value of length and depth in the healing area. The research was conducted to find the radiopaque and radiolucent patterns and the number of osteoblasts and osteoclasts. Results: This study resulted in a change in the radiograph pattern. Callus formation resulted in fracture areas with a smaller distance from day 0 to day 25. The bone healing process begins with granulation tissue formation, followed by the gradual replacement of the connective tissue and bone. This process is comparable to the increase in osteoblasts up to day 25, which blocks bone resorption. Osteoclasts regulate bone resorption, and their number increases after 10 and 17 days to replace bone formation. Osteoclasts decline after 25 days because osteoblasts inhibit them, which control bone formation. Conclusion: The conclusions were obtained there are changes in the radiograph pattern. The radiopaque increased while the radiolucent decreased; the osteoclast pattern tended to be stable and lowered while the osteoblasts increased during the fracture healing process. The correlation of all the factors is very closely related.

scholarly journals Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Rinaldo Florencio-Silva ◽  
Gisela Rodrigues da Silva Sasso ◽  
Estela Sasso-Cerri ◽  
Manuel Jesus Simões ◽  
Paulo Sérgio Cerri
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Current Data ◽  
Bone Diseases ◽  
Bone Homeostasis ◽  
Bone Biology ◽  
Structure And Functions

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

scholarly journals FEATURES OF DENTAL IMPLANTS IN THE COMPLEX TREATMENT OF PERIODONTAL DISEASE

2017 ◽  
Vol 6 ◽  
pp. 28-35
Author(s):  
Galina Prots ◽  
Mykola Rozhko ◽  
Vasyl Pjuryk ◽  
Irina Prots
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Dental Implants ◽  
Surgical Intervention ◽  
High Rate ◽  
Medication Prescription ◽  
Periodontal Tissues ◽  
Dental Implantation

Aim: To Improve the treatment of patients with partial edentia and chronic generalized periodontitis by including dental implantation to the complex of therapeutic measures. Materials and methods: There have been presented the results of 240 patients with varying severity degrees of generalized periodontitis who underwent surgery on periodontal tissues with dental implantation. The research was conducted at the OCH of Ivano-Frankivsk 2007–2017.To improve the efficiency for dental implants and periodontal surgical intervention is necessary to determine the quality of bone remodeling, identifying markers of bone tissue metabolism. Results: It was established that in 40,81 % patients the results of research showed markers of bone remodeling indicating a high rate of bone formation (25,12±2,23 ng / ml) and a slight increase in rate of resorption marker, which results in low rates of bone resorption (8,54±1,23 nmol/L). These patients were not prescribed with osteotropic drugs. 50,83 % of patients with osteopenia were noticed to manifest the formation of bone possible raise of bone resorption (10.82±1.34n/mole), which was the indication for antiresorptive medication prescription. In 8,36 % of patients with osteoporosis was observed inhibition of bone formation processes (18,05±2,08 ng / ml) and increased resorption indices (15,34±1,87 nmol/L). Medications that stimulate osteogenesis and prevent bone resorption were prescribed. Conclusions: When planning dental implants and periodontal surgical intervention it is necessary to identify markers of bone remodeling to assess the structural and functional state of bone tissue and prescribe osteotrophic drugs that promote positive postoperative period.

scholarly journals The Development of Molecular Biology of Osteoporosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8182
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Jingxian Jia
Keyword(s):  
Bone Resorption ◽  
Molecular Biology ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Cell Activity ◽  
Bone Cell ◽  
Bone Disorders ◽  
Molecular Aspects

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

scholarly journals Can Optimizing the Mechanical Environment Deliver a Clinically Significant Reduction in Fracture Healing Time?

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 691
Author(s):  
Jan Barcik ◽  
Devakara R. Epari
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Mechanical Stimulation ◽  
Callus Formation ◽  
Weight Bearing ◽  
Healing Process ◽  
Healing Time ◽  
Mechanical Environment ◽  
Clinically Significant ◽  
The Impact

The impact of the local mechanical environment in the fracture gap on the bone healing process has been extensively investigated. Whilst it is widely accepted that mechanical stimulation is integral to callus formation and secondary bone healing, treatment strategies that aim to harness that potential are rare. In fact, the current clinical practice with an initially partial or non-weight-bearing approach appears to contradict the findings from animal experiments that early mechanical stimulation is critical. Therefore, we posed the question as to whether optimizing the mechanical environment over the course of healing can deliver a clinically significant reduction in fracture healing time. In reviewing the evidence from pre-clinical studies that investigate the influence of mechanics on bone healing, we formulate a hypothesis for the stimulation protocol which has the potential to shorten healing time. The protocol involves confining stimulation predominantly to the proliferative phase of healing and including adequate rest periods between applications of stimulation.

scholarly journals Genes associated with inflammation and bone remodeling are highly expressed in the bone of patients with the early-stage cam-type femoroacetabular impingement

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Guanying Gao ◽  
Ruiqi Wu ◽  
Rongge Liu ◽  
Jianquan Wang ◽  
Yingfang Ao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Femoroacetabular Impingement ◽  
Early Stage ◽  
Control Group ◽  
Tissue Samples ◽  
Expression Levels ◽  
Normal Bone ◽  
Impingement Zone

Abstract Background Recent studies have shown high expression levels of certain inflammatory, anabolic, and catabolic genes in the articular cartilage from the impingement zone of the hips with femoroacetabular impingement (FAI), representing an increased metabolic state. Nevertheless, little is known about the molecular properties of bone tissue from the impingement zone of hips with FAI. Methods Bone tissue samples from patients with early-stage cam-type FAI were collected during hip arthroscopy for treatment of cam-type FAI. Control bone tissue samples were collected from six patients who underwent total hip replacement because of a femoral neck fracture. Quantitative real-time polymerase chain reaction (PCR) was performed to determine the gene expression associated with inflammation and bone remodeling. The differences in the gene expression in bone tissues from the patients with early-stage cam-type FAI were also evaluated based on clinical parameters. Results In all, 12 patients with early-stage cam-type FAI and six patients in the control group were included in this study. Compared to the control samples, the bone tissue samples from patients with FAI showed higher expression levels of interleukin-6 (IL-6), alkaline phosphatase (ALP), receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) (P < 0.05). IL-1 expression was detected only in the control group. On the other hand, there was no significant difference in IL-8 expression between the patients with FAI and the control group. The patients with FAI having a body mass index (BMI) of >24 kg/m2 showed higher ALP expression (P < 0.05). Further, the expression of IL-6 and ALP was higher in the patients with FAI in whom the lateral center-edge angle was >30° (P < 0.05). Conclusions Our results indicated the metabolic condition of bone tissues in patients with early-stage cam-type FAI differed from that of normal bone in the femoral head-neck junction. The expression levels of the genes associated with inflammation and bone remodeling were higher in the bone tissue of patients with early-stage cam-type FAI than in the patients with normal bone tissue.

Mechanisms of bone destruction in multiple myeloma: the importance of an unbalanced process in determining the severity of lytic bone disease.

1989 ◽  
Vol 7 (12) ◽  
pp. 1909-1914 ◽  
Author(s):  
R Bataille ◽  
D Chappard ◽  
C Marcelli ◽  
P Dessauw ◽  
J Sany ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
Cell Mass ◽  
Bone Destruction ◽  
Myeloma Cell ◽  
Bone Lesions ◽  
Mass Reduction

In order to clarify the mechanisms involved in the occurrence of lytic bone lesions (BL) in multiple myeloma (MM), we have compared the presenting myeloma-induced histological bone changes of 14 previously untreated MM patients with lytic BL with those of seven MM patients lacking lytic BL at presentation despite similar myeloma cell mass. A major unbalanced bone remodeling (increased bone resorption with normal to low bone formation) was the characteristic feature of patients presenting lytic BL. Furthermore, this unbalanced process was associated with a significant reduction of bone mass. Unexpectedly, a balanced bone remodeling (increase of both bone resorption and bone formation, without bone mass reduction) rather than a true lack of an excessive bone resorption was the usual feature of patients lacking lytic BL. Our current work clearly shows that a majority (72%) of patients with MM present an important unbalanced bone remodeling at diagnosis, leading to bone mass reduction and bone destruction (unbalanced MM). Some patients (20%) retain a balanced bone remodeling with initial absence of bone destruction (balanced MM). Few (8%) patients have pure osteoblastic MM without bone destruction.

scholarly journals Endogenous Production of n-3 Polyunsaturated Fatty Acids Promotes Fracture Healing in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yuhui Chen ◽  
He Cao ◽  
Dawei Sun ◽  
Changxin Lin ◽  
Liang Wang ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Fracture Healing ◽  
Histological Analysis ◽  
Callus Formation ◽  
Healing Process ◽  
Proximal Femoral Fracture ◽  
Fracture Repair ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
X Ray

Bone fracture is a global healthcare issue for high rates of delayed healing and nonunions. Although n-3 polyunsaturated fatty acid (PUFA) is considered as a beneficial factor for bone metabolism, only few studies till date focused on the effects of n-3 PUFAs on fracture healing. In this study, we investigated the effect of endogenous n-3 PUFAs on fracture healing by measuring femur fracture repair in bothfat-1transgenic mice and WT mice. Proximal femoral fracture model was established infat-1transgenic mice and WT mice, respectively, and then the fracture was analyzed by using X-ray, micro-computed tomography (micro-CT), and histological assessment at 7, 14, 21, 28, and 35 days after fixation. The results showed that compared with WT mice,fat-1mice exhibited acceleration in fracture healing through radiographic and histological analysis (18–21 days versus 21–28 days postfracture). Meanwhile, X-ray and micro-CT analysis that showed better remodeling callus formation were in thefat-1group compared to WT group. Furthermore, histological analysis revealed that endogenous n-3 PUFAs promoted local endochondral ossification and accelerated the remodeling of calcified calluses after fracture. In conclusion, the present study indicated that endogenously produced n-3 PUFAs promote fracture healing process and accelerate bone remodeling in mice, and supplementation of n-3 PUFAs was positively associated with fracture healing.

Can Time of Implant Placement influence Bone Remodeling?

2016 ◽  
Vol 17 (4) ◽  
pp. 270-274
Author(s):  
Caroline Freitas Rafael ◽  
Bernardo Passoni ◽  
Carlos Araújo ◽  
Maria A de Araújo ◽  
César Benfatti ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Remodeling ◽  
Healing Process ◽  
Bone Architecture ◽  
Implant Placement ◽  
Equal Rate ◽  
Average Analysis ◽  
Immediate Implants ◽  
Group 2 ◽  
Group 1

ABSTRACT Since the alveolar process is tissue “dental dependent,” after the extraction of the dental element, this process suffers some degree of atrophy during the healing process, which can be reduced with the installation of immediate implants, aiming to maintain the original bone architecture. The aim of this study was to investigate the influence of the time of implant placement on bone formation around them. Seven dogs were selected and randomly divided into two groups: Group 1, where implants were placed immediately after extraction of two lower premolars without flap elevation, and group 2, where implants were delayed by 4 months after extractions. Each group received 14 implants, and 4 months after the second surgery, the samples were processed and analyzed histomorphometrically. A mean average analysis and the Kruskal–Wallis test (p < 0.05) were performed. The buccal bone–implant contact (BIC) mean average was found larger in immediate implants (42.61%) compared with delayed implants (37.69%). Group 1 had statistically higher outcomes in bone formation and BIC on the buccal bone wall. It was concluded that performing immediate implants with the palatal approach technique and leaving a buccal GAP enables a higher or at least equal rate to BIC and bone area around them, when compared with delayed implants. Actually, the patients and dentists want to do a shorter treatment with satisfactory results, but it is necessary to understand whether different times of implant placement can influence the results and longevity of the treatment. How to cite this article Rafael CF, Passoni B, Araújo C, de Araújo MA, Benfatti C, Volpato C. Can Time of Implant Placement influence Bone Remodeling? J Contemp Dent Pract 2016;17(4):270-274.

Bortezomib Reduces Serum Dickkopf-1 and RANKL Concentrations and Normalizes Indices of Bone Remodeling in Patients with Relapsed Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 506-506
Author(s):  
Evangelos Terpos ◽  
Deborah Heath ◽  
Amin Rahemtulla ◽  
Kostas Zervas ◽  
Andrew Chantry ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Remodeling ◽  
Serum Levels ◽  
Response To Therapy ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Lytic Lesions ◽  
Tracp 5B ◽  
Dickkopf 1

Abstract Bortezomib is a proteasome inhibitor, which is currently indicated for the treatment of relapsed/refractory myeloma (MM). Although the anti-myeloma effect of bortezomib has been clearly demonstrated, its effect on bone metabolism is still unclear. There are recent reports that bortezomib increases serum alkaline phosphatase (ALP) activity, which is consistent with enhanced osteoblast function. The aim of this study was to evaluate the effect of bortezomib on bone turnover in 34 patients with relapsed MM. Bortezomib was given alone at a dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of a 3-week cycle for 4 cycles. Responders could continue for 4 more cycles, while non-responders could continue therapy with the addition of dexamethasone. The following serum indices were measured on day 1 of cycle 1, and then on day 21 of cycles 4 and 8: osteoblast inhibitor dickkopf-1 (DKK-1); osteoclast regulators: soluble RANKL (sRANKL) and osteoprotegerin (OPG); bone resorption markers: C-telopeptide of collagen type-I (CTX) and tartrate-resistant acid phosphatase type-5b (TRACP-5b); and bone formation markers: bone-specific ALP (bALP) and osteocalcin (OC). We also studied 33 healthy controls of similar gender and age. The objective response rate after 4 cycles of therapy was 66%: CR 8% and PR 58%. Sixteen responders and 3 non-responders continued on therapy for 4 more cycles. Myeloma patients at baseline had increased values of DKK-1 (p=0.007), sRANKL, sRANKL/OPG ratio, and both markers of bone resorption (p&lt;0.0001) when compared to controls. In contrast, bone formation as assessed by serum bALP and OC was significantly reduced (p&lt;0.001). There was a strong correlation between bone lytic disease and serum CTX (r=0.59, p&lt;0.01), and sRANKL (r=0.4, p=0.03). Patients with severe bone disease (&gt;9 lytic lesions, n=7) had elevated values of DKK-1 compared with all others (mean±SD: 223.4±264.4 ng/mL vs. 84±62.4 ng/mL; p=0.01). Moreover, serum levels of DKK-1 correlated with CTX levels (r=0.39, p=0.04), and weakly with bALP concentrations (r=−0.32, p=0.09). The administration of bortezomib produced a significant reduction of DKK-1 (p=0.035), sRANKL (p=0.01), CTX and TRACP-5b (p&lt;0.001) after 4 cycles, which was still seen after 8 cycles of treatment (p&lt;0.01). Bortezomib also produced a dramatic increase in both markers of bone formation, bALP and OC, after 4 and 8 cycles of therapy (p&lt;0.01). Responders tended to have lower initial levels of DKK-1 compared with non-responders. Patients who achieved a CR or vgPR after 4 cycles of bortezomib had greater elevation of bALP than all others: mean±SD of increase: 306.3%±556.9% vs. 45.8%±56.5%; p=0.02. It is of interest that 3/4 non responders also had an increase in bALP (mean: 39.6%) after 4 cycles of bortezomib. There was no other correlation between response to therapy and alteration of bone markers. No healing of the lytic lesions was observed even in CR patients. This study suggests that bortezomib reduces serum levels of DKK-1 and RANKL, irrespective of response to therapy, in patients with relapsed myeloma and thus leads to normalization of abnormal bone remodeling through the increase of bone formation and reduction of bone resorption.

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