The Effect of Aging on Bone Formation in Porous Hydroxyapatite: Biochemical and Histological Analysis

Inoue, Kohei; Ohgushi, Hajime; Yoshikawa, Takafumi; Okumura, M.; Sempuku, Takeo; Tamai, Susumu; Dohi, Yoshiko

doi:10.1359/jbmr.1997.12.6.989

Cited by 125 publications

(76 citation statements)

References 26 publications

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“…In this study we found, as others have reported, that aging is associated with a marked reduction in the osteogenic capacity of bone marrow, when compared with that of young rats (Tsuji et al 1990, Egrise et al 1992, Kahn et al 1995, Quarto et al 1995, Bergman et al 1996, Inoue et al 1997. However, this capacity can be stimulated by PGE 2 in both young and aging animals, peaking at a concentration of 100 nM (Weinreb et al 1999).…”

Section: Figure 11supporting

confidence: 78%

Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro

Keila¹,

Kelner²,

Weinreb³

2001

Journal of Endocrinology

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Prostaglandin E 2 (PGE 2 ) has been shown to exert a bone anabolic effect in young and adult rats. In this study we tested whether it possesses a similar effect on bone formation and bone mass in aging rats. Fifteen-month-old rats were injected daily with either PGE 2 at 5 mg/kg or vehicle for 14 days. PGE 2 treatment stimulated the rate of cancellous bone formation (a 5·5-fold increase in bone formation rate), measured by the incorporation of calcein into bone-forming surfaces at the tibial proximal metaphysis. This effect resulted in increased cancellous bone area (+54%) at the same site. Since PGE 2 treatment resulted in a much higher proportion of bone surface undergoing bone formation and thus lined with osteoblasts, we tested the hypothesis that PGE 2 stimulates osteoblast differentiation from bone marrow precursor cells both in vivo and in vitro. We found that ex vivo cultures of bone marrow stromal cells from rats injected for 2 weeks with PGE 2 at 5 mg/kg per day yielded more (4-fold) mineralized nodules and exhibited a greater (by 30-40%) alkaline phosphatase activity compared with cultures from vehicle-injected rats, attesting to a stimulation of osteoblastic differentiation by PGE 2 .We also compared the osteogenic capacity of bone marrow from aging (15-month-old) versus young (5-week-old) rats and its regulation by PGE 2 in vitro. Bone marrow stromal cell cultures from aging rats exhibited a greatly diminished osteogenic capacity, reflected in reduced nodule formation (6% of young animals) and lower alkaline phosphatase activity (60% of young animals). However, these parameters could be stimulated in both groups of animals by incubation with 10-100 nM PGE 2 . The magnitude of this stimulation was greater in cultures from aging rats (+550% vs +70% in nodule formation of aging compared with young rats).In conclusion, we demonstrate here that PGE 2 exerts a bone anabolic effect in aging rats, similar to the effect we and others have reported in young, growing rats. The PGE 2 -stimulated bone formation, which augments bone mass, most likely results from recruitment of osteoblasts from their bone marrow stromal precursors.

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Section: Figure 11supporting

confidence: 78%

Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro

Keila¹,

Kelner²,

Weinreb³

2001

Journal of Endocrinology

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“…However, age-dependent changes in the population of osteoprogenitor cells are discussed controversially. Recent results have given evidence of aging in marrow stromal progenitor cells [10,[40][41][42][43][44][45][46]. Other reports demonstrated that osteogenic progenitor cells were maintained during aging [47][48][49].…”

Section: Discussionmentioning

confidence: 99%

Fetal bone cells for tissue engineering

Montjovent

Burri

Mark

et al. 2004

Bone

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We envision the use of human fetal bone cells for engineered regeneration of adult skeletal tissue. A description of their cellular function is then necessary. To our knowledge, there is no description of human primary fetal bone cells treated with differentiation factors. The characterization of fetal bone cells is particularly important as the pattern of secreted proteins from osteoblasts has been shown to change during aging. In the first part of this work, human primary fetal bone cells were compared to adult bone cells and mesenchymal stem cells for their ability to proliferate and to differentiate into osteoblasts in vitro. Cell proliferation, gene expression of bone markers, alkaline phosphatase (ALP) activity, and mineralization were analyzed during a time-course study. In the second part of this paper, bone fetal cells behavior exposed to osteogenic factors is further detailed. The doubling time of fetal bone cells was comparable to mesenchymal stem cells but significantly shorter than for adult bone cells. Gene expression of cbfa-1, ALP, a1 chain of type I collagen, and osteocalcin were upregulated in fetal bone cells after 12 days of treatment, with higher inductions than for adult and mesenchymal stem cells. The increase of ALP enzymatic activity was stronger for fetal than for adult bone cells reaching a maximum at day 10, but lower than for mesenchymal stem cells. Importantly, the mineralization process of bone fetal cells started earlier than adult bone and mesenchymal stem cells. Proliferation of fetal and adult bone cells was increased by dexamethasone, whereas 1a,25-dihydroxyvitamin D 3 did not show any proliferative effect. Mineralization studies clearly demonstrated the presence of calcium deposits in the extracellular matrix of fetal bone cells. Nodule formation and calcification were strongly increased by the differentiation treatment, especially by dexamethasone. This study shows for the first time that human primary fetal bone cells could be of great interest for bone research, due to their fast growth rate and their ability to differentiate into mature osteoblasts. They represent an interesting and promising potential for therapeutic use in bone tissue engineering.

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“…*** these requirements; however, several studies are being conducted that will render these technologies available for their clinical application. Once this material is developed, studies on its safety, effectiveness and cost-benefit will be needed (Inoue et al, 1997;Orban et al).…”

Section: Introductionmentioning

confidence: 99%

Morphological Study of Bone Cranial in Athymic Mice

Ana

Ruvalcaba

Herrera³

et al. 2013

Int. J. Morphol.

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SUMMARY:The aim of our research was to create an osteogenic unit in the skulls of athymic mice; however, the first challenge we faced was to find sufficient and adequate data that would allow us to determine the morphological, immunohistochemical and microtopographical characteristics that could be used as normality standards in athymic mice skulls and, hence, a reference in the event of achieving the formation of de novo bone using the osteogenic unit we proposed. Knowing the normal bone morphology in the skull of athymic mice was a necessary precondition to develop subsequently an osteogenic unit possessing the Osteogenesis, Osteoinduction and Osteoconductivity that could be compared versus those in the normal bone during its formations and remodeling processes. Therefore, we conducted a pilot study to determine bone morphological characteristics in the skull of athymic mice by means of specific histological staining: hematoxylin-eosin and Von Kossa, for osteoid tissue and mineralized bone, and Masson Tri-chrome for ossified areas. We also use immunohistochemistry to detect bone formation markers: alkaline phosphatase resulting from osteoblastic activity stimulation, type 1 collagen a bonematrix structural protein; Osteopontine, a protein specifically synthesized by osteoblasts that favors cell proliferation and remodeling in bone defects; Osteocalcine, a peptide hormone produced by osteoblasts during bone formation; and, Runx 2, a transcription factor expressed by stem cells which stimulates bone differentiation. Likewise, we used electron microscopy on the newly formed tissue to determine the presence of organic deposits, such as calcium, phosphate and magnesium in bone tissue.

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The Effect of Aging on Bone Formation in Porous Hydroxyapatite: Biochemical and Histological Analysis

Cited by 125 publications

References 26 publications

Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro

Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro

Fetal bone cells for tissue engineering

Morphological Study of Bone Cranial in Athymic Mice

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