Reduced osteoblastic population and defective mineralization in osteopetrotic (op/op) mice

Sakagami, Naoko; Amizuka, Norio; Li, Minqi; Takeuchi, Kazunari; Hoshino, Masanori; Nakamura, Midori; Nozawa-Inoue, Kayoko; Udagawa, Nobuyuki; Maeda, Takeyasu

doi:10.1016/j.micron.2005.06.008

Cited by 50 publications

(41 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Without osteoclasts, osteoblastic population, osteoblastic bone formation and bone mineralization are markedly diminished in op/op mice, which lack the macrophage colony-stimulating factor [12,13]. One of our studies demonstrated that cell coupling between osteoclasts and preosteoblasts must take place for the parathyroid hormone-driven bone anabolic effect to occur [14].…”

Section: Introductionmentioning

confidence: 65%

“…In vivo animal studies have shown that bisphosphonate administration negatively affects mineral apposition rate, which suggests reduced osteoblast activity [15][16][17][18]. This may be due to hindrances in the "coupling phenomenon", the partnership with osteoclasts that seems to be necessary for osteoblastic activity during bone remodeling [12][13][14]. High-dose bisphosphonate administration disrupts the coupling between osteoclastic bone resorption and osteoblastic bone formation [34], and several in vivo studies have shown the effects of such disruption of cell coupling on osteoblasts [17,35].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of drug discontinuation after short-term daily alendronate administration on osteoblasts and osteocytes in mice

Tsuboi

Hasegawa

Yamamoto

et al. 2016

Histochem Cell Biol

Self Cite

View full text Add to dashboard Cite

In order to determine whether osteoclastic bone resorption is restarted after withdrawn of bisphosphonates, we conducted histological examinations on murine osteoclasts, osteoblasts and osteocytes after discontinuation of a daily regimen of alendronate (ALN) with a dosage of 1mg/kg/day for 10 days. After drug discontinuation, metaphyseal trabecular number and bone volume remained unaltered for the first 4 days. Osteoclast number did not increase, while the number of apoptotic osteoclasts was elevated. On the other hand, tissue non-specific alkaline phosphatase (ALPase)-immunoreactive area was markedly reduced after ALN discontinuation. In addition, osteocytes showed an atrophic profile with empty lacunar areas during and after ALN treatment. Interestingly, as early as 36 hrs after a single ALN injection, osteocytes show signs of atrophy despite the presence of active osteoblasts.Structured illumination microscopy system showed shortening of osteocytic cytoplasmic processes after drug cessation, suggesting a possible morphological and functional disconnection between osteocytes and osteoblasts.Taken together, it appears that osteoclastic bone resorption is not resumed after ALN discontinuation; also, osteoblasts and osteocytes hardly seem to recover once they are inactivated and atrophied by ALN. In summary, it seems that one must pay more attention to the responses of osteoblasts and osteocytes, rather focusing on the resuming of osteoclastic bone resorption after the ALN discontinuation.Tsuboi et al 5

show abstract

Section: Introductionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Effects of drug discontinuation after short-term daily alendronate administration on osteoblasts and osteocytes in mice

Tsuboi

Hasegawa

Yamamoto

et al. 2016

Histochem Cell Biol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Epoxy resin sections of undecalcified specimens were incubated with an aqueous solution of silver nitrate until black staining of the bone tissue was discernible under light microscopy [42].…”

Section: Von Kossa Stainingmentioning

confidence: 99%

Altered distribution of bone matrix proteins and defective bone mineralization in klotho-deficient mice

Sasaki

Hasegawa

Yamada

et al. 2013

Bone

Self Cite

View full text Add to dashboard Cite

In an attempt to identify the histological properties of the klotho-deficient (kl/kl) bone matrix, bone mineralization and the localization of Ca 2+ -binding bone matrix proteins -osteocalcin, dentin matrix protein-1 (DMP-1) and matrix Gla protein (MGP) -were examined in kl/kl tibiae.While a widespread osteocalcin staining could be verified in the wild-type bone matrix, localization of the same protein in kl/kl tibiae seemed rather restricted to osteocytes with only a faint staining of the whole bone matrix. In wild-type mice, MGP immunoreactivity was present at the junction between the epiphyseal bone and cartilage, and at the insertion of the cruciate ligaments. In kl/kl mice, however, MGP was seen around the cartilaginous cores of the metaphyseal trabeculae and in the periphery of some cells of the bone surface. DMP-1 was identified in the osteocytic canalicular system of wild-type tibiae, but in kl/kl tibiae this protein was mostly found in the osteocytic lacunae and in the periphery of some cells of the bone surface.Mineralization of the kl/kl bone seemed somewhat defective, with broad unmineralized areas within its matrix. In these areas, mineralized osteocytes along with their lacunae and osteocytic cytoplasmic processes were found to have intense osteocalcin and DMP-1 staining. Taken together, it might be that the excessive production of Ca 2+ -binding molecules such as osteocalcin and DMP-1 by osteocytes concentrates mineralization around such cells, disturbing the completeness of mineralization in the kl/kl bone matrix. words

show abstract

“…Longitudinal sections of tibial epiphyseal cartilage embedded in epoxy resin were incubated with an aqueous solution of nitric silver until calcified matrix is visible in dark brown color, as reported elsewhere (22).…”

Section: Intense Mmp-13 Immunoreactivity In the Lower Region Of The Mmentioning

confidence: 99%

Histochemical aspects of the vascular invasion at the erosion zone of the epiphyseal cartilage in MMP-9-deficient mice

et al. 2013

Self Cite

View full text Add to dashboard Cite

We have histologically examined vascular invasion and calcification of the hypertrophic zone during endochondral ossification in matrix metalloproteinase (MMP)-9 deficient (MMP-9 −/− ) mice and in their littermates at 3 days, 3 weeks and 6 weeks after birth. Capillaries and osteoclasts at the chondro-osseous junction showed an intense MMP-9 immunopositivity, suggesting that they recognize chemical properties of cartilaginous matrices, and then release MMP-9 for cartilage degradation. CD31-positive capillaries and tartrate-resistant acid phosphatase-reactive osteoclasts could be found in the close proximity in the region of chondro-osseous junction in MMP-9 −/− mice, while in wild-type mice, vascular invasion preceded osteoclastic migration into the epiphyseal cartilage. Although MMP-9 −/− mice revealed larger hypertrophic zones, the index of calcified area was significantly smaller in MMP-9 −/− mice. Interestingly, the lower layer of the MMP-9 −/− hypertrophic zone showed intense MMP-13 staining, which could not be observed in wild-type mice. This indicates that MMP-13 may compensate for MMP-9 deficiency at that specific region, but not to a point at which the deficiency could be completely rescued. In conclusion, it seems that MMP-9 is the optimal enzyme for cartilage degradation during endochondral ossification by controlling vascular invasion and subsequent osteoclastic migration.Endochondral ossification enables the longitudinal growth of long bones, keeping the balance between chondrocyte proliferation and differentiation (i.e., appositional and interstitial growth) and vascular invasion into cartilage prior to bone deposition (12,27). The length of the hypertrophic zone appears to be maintained by two mechanisms: 1) the rate at which chondrocytes enter the hypertrophic phenotype and 2) the pace at which vascular endothelial cells invade the hypertrophic zone of the cartilage. After the formation of calcified cartilage matrices, the process of endochondral ossification involves a well-defined series of events in which osteogenic and osteoclastic cells replace calcified cartilage for bone (2). At an erosion zone, vascular endothelial cells invade and collapse incompletely-calcified transverse partitions of cartilage matrix, making a way for osteoclastic and osteoblastic migration. On the other hand, the longitudinal intercolumnar septae are

show abstract

Reduced osteoblastic population and defective mineralization in osteopetrotic (op/op) mice

Cited by 50 publications

References 27 publications

Effects of drug discontinuation after short-term daily alendronate administration on osteoblasts and osteocytes in mice

Effects of drug discontinuation after short-term daily alendronate administration on osteoblasts and osteocytes in mice

Altered distribution of bone matrix proteins and defective bone mineralization in klotho-deficient mice

Histochemical aspects of the vascular invasion at the erosion zone of the epiphyseal cartilage in MMP-9-deficient mice

Contact Info

Product

Resources

About