Endocrine function of osteocytes

2016 ◽  
Vol 25 (02) ◽  
pp. 62-68
Author(s):  
T. Yorgan ◽  
T. Schinke
Keyword(s):  
Bone Formation ◽  
Matrix Protein ◽  
Vascular System ◽  
Bone Matrix ◽  
Endocrine Function ◽  
Whole Body ◽  
Dependent Manner ◽  
Phosphate Homeostasis ◽  
Target Organs ◽  
Additional Influence

SummaryOsteocytes represent the most abundant cell type of the skeletal system. They have access to a large cellular surface area within the lacuno-canalicular network. This network additionally provides connection to the vascular system, a prerequisite for secretion of endocrine regulators into the circulation. The best established endocrine function of the osteocyte network is the regulation of phosphate homeostasis by secretion of Fgf23, a hormone inhibiting renal phosphate reabsorption. Recently, several additional osteocyte-derived factors have been suggested to influence phosphate homeostasis, either directly or in an Fgf23-dependent manner. Moreover, osteocytes are also the major producers of Wnt signaling modulators, such as Sclerostin or Dkk1. Since these molecules primarily act as inhibitors of bone formation, there might be an additional influence of osteocyte-derived molecules on glucose handling and energy metabolism. In fact, osteocalcin, a long-known bone matrix protein and biomarker of bone formation, is now considered to act as a hormone controlling insulin production by pancreatic β-cells and insulin sensitivity of target organs. Since the endocrine functions of osteocytes are only beginning to be uncovered, it appears likely that additional osteocyte-derived molecules with systemic influences on whole body homeostasis might be identified in the future.

scholarly journals DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis

2006 ◽  
Vol 38 (11) ◽  
pp. 1248-1250 ◽  
Author(s):  
Bettina Lorenz-Depiereux ◽  
Murat Bastepe ◽  
Anna Benet-Pagès ◽  
Mustapha Amyere ◽  
Janine Wagenstaller ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Matrix Protein ◽  
Bone Matrix ◽  
Phosphate Homeostasis ◽  
Bone Matrix Protein

scholarly journals Type XII collagen regulates osteoblast polarity and communication during bone formation

2011 ◽  
Vol 193 (6) ◽  
pp. 1115-1130 ◽  
Author(s):  
Yayoi Izu ◽  
Mei Sun ◽  
Daniela Zwolanek ◽  
Guido Veit ◽  
Valerie Williams ◽  
...  
Keyword(s):  
Bone Formation ◽  
Matrix Protein ◽  
Bone Matrix ◽  
Cell Interaction ◽  
Matrix Deposition ◽  
Extensive Cell ◽  
Triple Helices ◽  
Delayed Maturation ◽  
Bone Deposition ◽  
Quality Type

Differentiated osteoblasts are polarized in regions of bone deposition, demonstrate extensive cell interaction and communication, and are responsible for bone formation and quality. Type XII collagen is a fibril-associated collagen with interrupted triple helices and has been implicated in the osteoblast response to mechanical forces. Type XII collagen is expressed by osteoblasts and localizes to areas of bone formation. A transgenic mouse null for type XII collagen exhibits skeletal abnormalities including shorter, more slender long bones with decreased mechanical strength as well as altered vertebrae structure compared with wild-type mice. Col12a−/− osteoblasts have decreased bone matrix deposition with delayed maturation indicated by decreased bone matrix protein expression. Compared with controls, Col12a−/− osteoblasts are disorganized and less polarized with disrupted cell–cell interactions, decreased connexin43 expression, and impaired gap junction function. The data demonstrate important regulatory roles for type XII collagen in osteoblast differentiation and bone matrix formation.

scholarly journals Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yang Chen ◽  
Sujuan Yang ◽  
Sara Lovisa ◽  
Catherine G. Ambrose ◽  
Kathleen M. McAndrews ◽  
...  
Keyword(s):  
Bone Formation ◽  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Bone Matrix ◽  
Whole Body ◽  
Type I ◽  
Sequencing Analysis ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Skeletal Defects

AbstractType I collagen (Col1) is the most abundant protein in mammals. Col1 contributes to 90% of the total organic component of bone matrix. However, the precise cellular origin and functional contribution of Col1 in embryogenesis and bone formation remain unknown. Single-cell RNA-sequencing analysis identifies Fap+ cells and Fsp1+ cells as the major contributors of Col1 in the bone. We generate transgenic mouse models to genetically delete Col1 in various cell lineages. Complete, whole-body Col1 deletion leads to failed gastrulation and early embryonic lethality. Specific Col1 deletion in Fap+ cells causes severe skeletal defects, with hemorrhage, edema, and prenatal lethality. Specific Col1 deletion in Fsp1+ cells results in Osteogenesis Imperfecta-like phenotypes in adult mice, with spontaneous fractures and compromised bone healing. This study demonstrates specific contributions of mesenchymal cell lineages to Col1 production in organogenesis, skeletal development, and bone formation/repair, with potential insights into cell-based therapy for patients with Osteogenesis Imperfecta.

scholarly journals Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation

2000 ◽  
Vol 151 (2) ◽  
pp. 311-320 ◽  
Author(s):  
Marilena Marzia ◽  
Natalie A. Sims ◽  
Susanne Voit ◽  
Silvia Migliaccio ◽  
Anna Taranta ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Osteoblast Differentiation ◽  
Matrix Protein ◽  
Bone Matrix ◽  
Osteogenic Cells ◽  
Alp Activity ◽  
Pthrp Receptor ◽  
Bone Matrix Protein

c-src deletion in mice leads to osteopetrosis as a result of reduced bone resorption due to an alteration of the osteoclast. We report that deletion/reduction of Src expression enhances osteoblast differentiation and bone formation, contributing to the increase in bone mass. Bone histomorphometry showed that bone formation was increased in Src null compared with wild-type mice. In vitro, alkaline phosphatase (ALP) activity and nodule mineralization were increased in primary calvarial cells and in SV40-immortalized osteoblasts from Src−/− relative to Src+/+ mice. Src-antisense oligodeoxynucleotides (AS-src) reduced Src levels by ∼60% and caused a similar increase in ALP activity and nodule mineralization in primary osteoblasts in vitro. Reduction in cell proliferation was observed in primary and immortalized Src−/− osteoblasts and in normal osteoblasts incubated with the AS-src. Semiquantitative reverse transcriptase-PCR revealed upregulation of ALP, Osf2/Cbfa1 transcription factor, PTH/PTHrP receptor, osteocalcin, and pro-alpha 2(I) collagen in Src-deficient osteoblasts. The expression of the bone matrix protein osteopontin remained unchanged. Based on these results, we conclude that the reduction of Src expression not only inhibits bone resorption, but also stimulates osteoblast differentiation and bone formation, suggesting that the osteogenic cells may contribute to the development of the osteopetrotic phenotype in Src-deficient mice.

scholarly journals A decrease in NAD+ contributes to the loss of osteoprogenitors and bone mass with aging

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ha-Neui Kim ◽  
Filipa Ponte ◽  
Aaron Warren ◽  
Rebecca Ring ◽  
Srividhya Iyer ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Bone Matrix ◽  
Cell Senescence ◽  
Dependent Manner ◽  
Nicotinamide Riboside ◽  
Age Related ◽  
Foxo Transcription Factors ◽  
Old Mice ◽  
Osteoblast Progenitors

AbstractAge-related osteoporosis is caused by a deficit in osteoblasts, the cells that secrete bone matrix. The number of osteoblast progenitors also declines with age associated with increased markers of cell senescence. The forkhead box O (FoxO) transcription factors attenuate Wnt/β-catenin signaling and the proliferation of osteoprogenitors, thereby decreasing bone formation. The NAD+-dependent Sirtuin1 (Sirt1) deacetylates FoxOs and β-catenin in osteoblast progenitors and, thereby, increases bone mass. However, it remains unknown whether the Sirt1/FoxO/β-catenin pathway is dysregulated with age in osteoblast progenitors. We found decreased levels of NAD+ in osteoblast progenitor cultures from old mice, associated with increased acetylation of FoxO1 and markers of cell senescence. The NAD+ precursor nicotinamide riboside (NR) abrogated FoxO1 and β-catenin acetylation and several marker of cellular senescence, and increased the osteoblastogenic capacity of cells from old mice. Consistent with these effects, NR administration to C57BL/6 mice counteracted the loss of bone mass with aging. Attenuation of NAD+ levels in osteoprogenitor cultures from young mice inhibited osteoblastogenesis in a FoxO-dependent manner. In addition, mice with decreased NAD+ in cells of the osteoblast lineage lost bone mass at a young age. Together, these findings suggest that the decrease in bone formation with old age is due, at least in part, to a decrease in NAD+ and dysregulated Sirt1/FoxO/β-catenin pathway in osteoblast progenitors. NAD+ repletion, therefore, represents a rational therapeutic approach to skeletal involution.

scholarly journals A non-immunological role for γ-interferon–inducible lysosomal thiol reductase (GILT) in osteoclastic bone resorption

2021 ◽  
Vol 7 (17) ◽  
pp. eabd3684
Author(s):  
Benjamin W. Ewanchuk ◽  
Corey R. Arnold ◽  
Dale R. Balce ◽  
Priyatha Premnath ◽  
Tanis L. Orsetti ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Cysteine Protease ◽  
Antigen Processing ◽  
Matrix Protein ◽  
Direct Reduction ◽  
Bone Matrix ◽  
Cathepsin K ◽  
Dependent Manner ◽  
Thiol Reductase ◽  
Γ Interferon

The extracellular bone resorbing lacuna of the osteoclast shares many characteristics with the degradative lysosome of antigen-presenting cells. γ-Interferon–inducible lysosomal thiol reductase (GILT) enhances antigen processing within lysosomes through direct reduction of antigen disulfides and maintenance of cysteine protease activity. In this study, we found the osteoclastogenic cytokine RANKL drove expression of GILT in osteoclast precursors in a STAT1-dependent manner, resulting in high levels of GILT in mature osteoclasts, which could be further augmented by γ-interferon. GILT colocalized with the collagen-degrading cysteine protease, cathepsin K, suggesting a role for GILT inside the osteoclastic resorption lacuna. GILT-deficient osteoclasts had reduced bone-resorbing capacity, resulting in impaired bone turnover and an osteopetrotic phenotype in GILT-deficient mice. We demonstrated that GILT could directly reduce the noncollagenous bone matrix protein SPARC, and additionally, enhance collagen degradation by cathepsin K. Together, this work describes a previously unidentified, non-immunological role for GILT in osteoclast-mediated bone resorption.

scholarly journals Sclerostin and Osteocalcin: Candidate Bone-Produced Hormones

2021 ◽  
Vol 12 ◽  
Author(s):  
Jialiang S. Wang ◽  
Courtney M. Mazur ◽  
Marc N. Wein
Keyword(s):  
Energy Homeostasis ◽  
Matrix Protein ◽  
Mineral Metabolism ◽  
Bone Mineralization ◽  
Cell Types ◽  
Endocrine Function ◽  
Future Research ◽  
Current State ◽  
Target Organs ◽  
Endocrine Hormone

In addition to its structural role, the skeleton serves as an endocrine organ that controls mineral metabolism and energy homeostasis. Three major cell types in bone - osteoblasts, osteoclasts, and osteocytes – dynamically form and maintain bone and secrete factors with systemic activity. Osteocalcin, an osteoblast-derived factor initially described as a matrix protein that regulates bone mineralization, has been suggested to be an osteoblast-derived endocrine hormone that regulates multiple target organs including pancreas, liver, muscle, adipose, testes, and the central and peripheral nervous system. Sclerostin is predominantly produced by osteocytes, and is best known as a paracrine-acting regulator of WNT signaling and activity of osteoblasts and osteoclasts on bone surfaces. In addition to this important paracrine role for sclerostin within bone, sclerostin protein has been noted to act at a distance to regulate adipocytes, energy homeostasis, and mineral metabolism in the kidney. In this article, we aim to bring together evidence supporting an endocrine function for sclerostin and osteocalcin, and discuss recent controversies regarding the proposed role of osteocalcin outside of bone. We summarize the current state of knowledge on animal models and human physiology related to the multiple functions of these bone-derived factors. Finally, we highlight areas in which future research is expected to yield additional insights into the biology of osteocalcin and sclerostin.

Multiple Myeloma Cell-Osteoblast Interaction Results in Impaired Bone Formation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4764-4764
Author(s):  
Sonia Vallet ◽  
Teru Hideshima ◽  
Samantha Pozzi ◽  
Nileshwari Vaghela ◽  
Gaurav Gharti-Chhetri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Formation ◽  
Cell Lines ◽  
Bone Matrix ◽  
Type I ◽  
Dependent Manner ◽  
Alizarin Red ◽  
Matrix Mineralization ◽  
Osteolytic Bone Disease

Abstract Osteolytic bone disease is a common complication of multiple myeloma (MM) resulting from uncoupled bone remodeling due to enhanced bone resorption and reduced bone formation. Bone formation is a complex process requiring functionally mature osteoblasts (OB). Mesenchymal stem cells differentiate into mature OB and following an active period of bone matrix synthesis lasting 1–2 weeks, they finally differentiate into inactive bone-lining cells or osteocytes. Although several studies have demonstrated that MM cells inhibit osteoblastogenesis via secretion of DKK1, a Wnt-pathway antagonist, the functional sequelae of interaction of mature OB with MM cells remains to be elucidated. Here, we studied the morphological and functional consequences induced by MM cells interacting with mature OB. Mature OB were generated from MM patients’ bone marrow mononuclear cells by cultivation in differentiation media consisting of αMEM with 20% fetal bovine serum, β-glycerol phosphate (2.16 mg/ml), ascorbic acid (0.05 mg/ml) and dexamethasone (10 nM). These mature OBs were alkaline phosphatase (ALP) positive and secreted and mineralized bone matrix, as demonstrated by Alizarin Red staining. MM cell lines INA6 and MM1.S were co-cultured with mature OB at a 5:1 ratio for 2, 4 and 7 days in OB differentiation media and bone marrow stromal cells (BMSC) were used as negative controls. After 4 days of co-culture, we observed phenotypic changes featured by acquisition of a spindle-like shape with reduced ALP staining in OB. In contrast, OB alone were intensely ALP-positive and cuboidal-shaped cells. Co-culture with INA-6 MM cells induced a reduction in ALP enzymatic activity in a time-dependent manner by 28% (± 10%) at day 2 and 72% (± 5%) at day 4 (p<0.05), respectively, whereas co-culture with MM1.S induced a 38% (± 5%) reduction after 4 days. Other MM cell lines induced similar effects. We then verified OB activity by assessing osteocalcin release and matrix mineralization. Importantly, osteocalcin secretion was completely abrogated in the presence of INA6, while MM1.S reduced it by 50% as early as day 2 (p<0.05). Moreover, Alizarin red staining demonstrated an impairment of matrix mineralization after 7 days of co-culture. Reduced OB function in the presence of MM cells was further confirmed by downregulation of Type-I collagen expression in OB. These effects were associated with only modest (10%) OB apoptosis as demonstrated by APO2.7 staining after 4 days of co-culture compared to OB alone. These phenotypic and functional sequelae on OB were not induced by co-culture supernatants, suggesting the requirement for direct MM cell/OB contact. These results therefore suggest that MM cell/mature OB interactions result in inhibition of bone formation by inactivation of mature OB. Ongoing studies are characterizing the mechanism by which MM cells induce OB inactivation and whether these changes affect the OC compartment. These studies of MM cell-OB interactions will form the basis for evaluation of novel agents with anabolic effects on the bone in the future.

scholarly journals The Effect of Hypertension on Hearing Sense

2018 ◽  
Vol 1 (1) ◽  
pp. 69
Author(s):  
A.C Romdhoni
Keyword(s):  
Hearing Loss ◽  
Vascular System ◽  
The Body ◽  
Whole Body ◽  
Target Organs ◽  
High Prevalence ◽  
Important Health ◽  
Ionic Changes ◽  
The Relationship ◽  
Inner Ear Damage

Hypertension is an important health problem because it has a high prevalence and can cause damage to target organs. The relationship between hypertension and hearing loss is not difficult to understand, when blood pressure becomes high blood vessel damage occurs. Hearing loss cases caused by hypertension are considerable, in America 64 million people aged 18 to 75 years suffer from hypertension, 40% with hearing loss. This damage is not centered on one area of the body, but the whole body is also affected, including the ears. The incidence of hearing loss in hypertension is due to the occurrence of inner ear damage due to high pressure in the vascular system, changes in microcirculation and the occurrence of ionic changes.

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