Bone remodeling in the longest living rodent, the naked mole-rat: Interelement variation and the effects of reproduction.
The pattern of bone remodeling of one of the most peculiar mammals in the world, the naked mole-rat (NMR), was assessed. NMRs are known for their long lifespans among rodents and for having low metabolic rates. We assessed long-term in vivo bone labeling of subordinate individuals, as well as the patterns of bone resorption and bone remodeling in a large sample including reproductive and non-reproductive individuals (n = 70).
Over 268 undecalcified thin cross-sections from the midshaft of humerus, ulna, femur and tibia were analyzed with confocal fluorescence and polarized light microscopy. Fluorochrome analysis revealed low osteogenesis, scarce bone resorption and infrequent formation of secondary osteons (Haversian systems) (i.e., slow bone turnover), thus most likely reflecting the low metabolic rates of this species.
Montoya-Sanhueza G;Bennett NC;Oosthuizen MK;Dengler-Crish CM;Chinsamy A
Journal Of Anatomy
2021
2021-02-07
Journal Article
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Bone remodeling in the longest living rodent, the naked mole-rat: Interelement variation and the effects of reproduction.
Bone resorption; Heterocephalus glaber; Female breeder; Haversian systems; Secondary osteons; Secondary reconstruction
The pattern of bone remodeling of one of the most peculiar mammals in the world, the naked mole-rat (NMR), was assessed. NMRs are known for their long lifespans among rodents and for having low metabolic rates. We assessed long-term in vivo bone labeling of subordinate individuals, as well as the patterns of bone resorption and bone remodeling in a large sample including reproductive and non-reproductive individuals (n = 70). Over 268 undecalcified thin cross-sections from the midshaft of humerus, ulna, femur and tibia were analyzed with confocal fluorescence and polarized light microscopy. Fluorochrome analysis revealed low osteogenesis, scarce bone resorption and infrequent formation of secondary osteons (Haversian systems) (i.e., slow bone turnover), thus most likely reflecting the low metabolic rates of this species. Secondary osteons occurred regardless of reproductive status. However, considerable differences in the degree of bone remodeling were found between breeders and non-breeders. Pre-reproductive stages (subordinates) exhibited quite stable skeletal homeostasis and bone structure, although the attainment of sexual maturity and beginning of reproductive cycles in female breeders triggered a series of anabolic and catabolic processes that up-regulate bone turnover, most likely associated with the increased metabolic rates of reproduction. Furthermore, bone remodeling was more frequently found in stylopodial elements compared to zeugopodial elements. Despite the limited bone remodeling observed in NMRs, the variation in the pattern of skeletal homeostasis (interelement variation) reported here represents an important aspect to understand the skeletal dynamics of a small mammal with low metabolic rates. Given the relevance of the remodeling process among mammals, this study also permitted the comparison of such process with the well-documented histomorphology of extinct therapsids (i.e., mammalian precursors), thus evidencing that bone remodeling and its endocortical compartmentalization represent ancestral features among the lineage that gave rise to mammals. It is concluded that other factors associated with development (and not uniquely related to biomechanical loading) can also have an important role in the development of bone remodeling.
Montoya-Sanhueza G;Bennett NC;Oosthuizen MK;Dengler-Crish CM;Chinsamy A
Journal Of Anatomy
2021
2021-02-07
journalArticle
<a href="http://doi.org/10.1111/joa.13404" target="_blank" rel="noreferrer noopener">10.1111/joa.13404</a>
Baculovirus-expressed vitamin D-binding protein-macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D-3 does not influence this activity
activating factor (DBP-maf); albumin; alpha-fetoprotein; Biochemistry & Molecular Biology; bone resorption; bone resorption; Cell Biology; cells; family; gc-globulin; group-specific component; identification; in-vitro; member; osteoclast activation; recombinant DBP-maf; vitamin D-binding protein (DBP); vitamin D-binding protein macrophage
Vitamin D-binding protein (DBP) is a multi-functional serum protein that is converted to vitamin D-binding protein-macrophage activating factor (DBP-maf) by post-translational modification. DBP-maf is a new cytokine that mediates bone resorption by activating osteoclasts, which are responsible for resorption of bone. Defective osteoclast activation leads to disorders like osteopetrosis, characterized by excessive accumulation of bone mass. Previous studies demonstrated that two nonallelic mutations in the rat with osteopetrosis have independent defects in the cascade involved in the conversion of DBP to DBP-maf. The skeletal defects associated with osteopetrosis are corrected in these mutants with in vivo DBP-maf treatment. This study evaluates the effects of various forms of DBP-maf (native, recombinant, and 25-hydroxyvitamin D-3 bound) on osteoclast function in vitro in order to determine some of the structural requirements of this protein that relate to bone resorbing activities. Osteoclast activity was determined by evaluating pit formation using osteoclasts, isolated from the long bones of newborn rats, incubated on calcium phosphate coated, thin film, Ostologic MultiTest Slides. Incubation of osteoclasts with ex vivo generated native DBP-maf resulted in a dose dependent, statistically significant, activation of the osteoclasts. The activation was similar whether or not the vitamin D binding site of the DBP-maf was occupied. The level of activity in response to DBP-maf was greater than that elicited by optimal doses of other known stimulators (PTH and 1,25(OH)(2)D-3) of osteoclast function. Furthermore, another potent macrophage activating factor, interferon-gamma, had no effect on osteoclast activity. The activated form of a full length recombinant DBP, expressed in E. coli showed no activity in the in vitro assay. Contrary to this finding, baculovirus-expressed recombinant DBP-maf demonstrated significant osteoclast activating activity. The normal conversion of DBP to DBP-maf requires the selective removal of galactose and sialic acid from the third domain of the protein. Hence, the differential effects of the two recombinant forms of DBP-maf is most likely related to glycosylation; E. coli expressed recombinant DBP is non-glycosylated, whereas the baculovirus expressed form is glycosylated. These data support the essential role of glycosylation for the osteoclast activating property of DBP-mai. J. Cell. Biochem. 81:535-546, 2001. (C) 2001 Wiley-Liss, Inc.
Swamy N; Ghosh S; Schneider G B; Ray R
Journal of Cellular Biochemistry
2001
2001
Journal Article
<a href="http://doi.org/10.1002/1097-4644(20010601)81:3%3C535::aid-jcb1067%3E3.0.co;2-6" target="_blank" rel="noreferrer noopener">10.1002/1097-4644(20010601)81:3%3C535::aid-jcb1067%3E3.0.co;2-6</a>
Role of inflammation in the aging bones.
*Models; Aging; Aging/*physiology; Animals; Biological; Bone adaptation; Bone and Bones/cytology/immunology/*physiopathology; Bone Marrow Cells/physiology; Bone resorption; Cell Differentiation/*physiology; Cumulative Trauma Disorders/physiopathology; Humans; Inflammation; Inflammation/*physiopathology; Macrophages; Macrophages/*physiology; Osteoblasts; Osteoblasts/*physiology; Osteoclasts; Osteoclasts/*physiology
Chronic inflammation in aging is characterized by increased inflammatory cytokines, bone loss, decreased adaptation, and defective tissue repair in response to injury. Aging leads to inherent changes in mesenchymal stem cell (MSC) differentiation, resulting in impaired osteoblastogenesis. Also, the pro-inflammatory cytokines increase with aging, leading to enhanced myelopoiesis and osteoclastogenesis. Bone marrow macrophages (BMMs) play pivotal roles in osteoblast differentiation, the maintenance of hematopoietic stem cells (HSCs), and subsequent bone repair. However, during aging, little is known about the role of macrophages in the differentiation and function of MSC and HSC. Aged mammals have higher circulating pro-inflammatory cytokines than young adults, supporting the hypothesis of increased inflammation with aging. This review will aid in the understanding of the potential role(s) of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in differentiation and function of osteoblasts and osteoclasts in relation to aging.
Abdelmagid Samir M; Barbe Mary F; Safadi Fayez F
Life sciences
2015
2015-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.lfs.2014.11.011" target="_blank" rel="noreferrer noopener">10.1016/j.lfs.2014.11.011</a>