Recruitment and Proliferative Responses of Osteoblasts After Mechanical Loading In Vivo Determined Using Sustained-Release Bromodeoxyuridine

Turner, Charles H.; Owan, Ichiro; Iii, TV Alvey; Hulman, James F.; Hock, Janet M.

doi:10.1016/s8756-3282(98)00041-6

Cited by 106 publications

(129 citation statements)

References 14 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…Whilst little is known regarding the recruitment of stem cells from the niche to a site of loading, these data are supported by the in vivo observations by Turner et al [28], of mechanical loading-induced recruitment of proliferating cells from the marrow to the bone surface enhancing bone formation. Robust proliferative effects of statically cultured osteocyte conditioned media upon bone marrow progenitors and osteoblasts has been demonstrated previously [29], however the enhanced proliferative response observed with the application of mechanically stimulated osteocyte conditioned media indicates that these molecules are mechanically regulated.…”

Section: Discussionmentioning

confidence: 78%

See 1 more Smart Citation

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

Brady

O’Brien

Hoey

2015

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

ABSTRACT:Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors.

show abstract

Section: Discussionmentioning

confidence: 78%

“…A potent regulator of bone anabolism is mechanical loading [10]. This involves a complex interplay between multiple cell types, with osteogenic cues believed to be propagated to osteoprogenitors via upstream mechanosensor cells.…”

Section: Introductionmentioning

confidence: 99%

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

Brady

O’Brien

Hoey

2015

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

show abstract

“…However, the robust regeneration of both functional hematopoietic and osteocytic target tissues (up to 50% of bone cells in some sections) suggests a physiologically important progenitor cell response rather than a rare stochastic event that typifies most instances of ''stem cell plasticity'' (37). This striking engraftment of marked progenitor cells might be explained by observations that murine osteoblasts can be recruited from progenitor cells in only a few days in response to changes in stressful stimuli (38), such as chemotherapy or irradiation. Indeed, the robust osteopoietic engraftment we observed may well depend on the marrow-ablative effects of radiation (39), although this relationship will need to be assessed in carefully controlled competitive repopulation experiments.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation

Dominici

Pritchard

Garlits

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

142

124

View full text Add to dashboard Cite

Bone and bone marrow are closely aligned physiologic compartments, suggesting that these tissues may represent a single functional unit with a common bone marrow progenitor that gives rise to both osteoblasts and hematopoietic cells. Although reports of multilineage engraftment by a single marrow-derived stem cell support this idea, more recent evidence has challenged claims of stem cell transdifferentiation and therefore the existence of a multipotent hematopoietic͞osteogenic progenitor cell. Using a repopulation assay in mice, we show here that gene-marked, transplantable marrow cells from the plastic-nonadherent population can generate both functional osteoblasts͞osteocytes and hematopoietic cells. Fluorescent in situ hybridization for the X and Y chromosomes and karyotype analysis of cultured osteoblasts confirmed the donor origin of these cells and excluded their generation by a fusion process. Molecular analysis demonstrated a common retroviral integration site in clonogenic hematopoietic cells and osteoprogenitors from each of seven animals studied, establishing a shared clonal origin for these ostensibly independent cell types. Our findings indicate that the bone marrow contains a primitive cell able to generate both the hematopoietic and osteocytic lineages. Its isolation and characterization may suggest novel treatments for genetic bone diseases and bone injuries.

show abstract

“…Prior to processing, tissue slides were exposed to 0.05% pepsin in 0.1 N HCl for 30 min at 37°C. Slides were then placed in citrate buffer, heated at 50°C for 20 min for heat induced target antigen retrieval, and incubated with 1:100 primary antibody to BrdU (Dako Corp., Carpenteria, CA) [31,32]. To identify actively proliferating cells, nuclei that had incorporated BrdU were detected using the Dako EnVision+ System, Peroxidase system (Dako Corp., Carpenteria, CA.)…”

Section: Measurement Of Bromodeoxyuridine Incorporation In Decalcifiementioning

confidence: 99%

CCAAT/Enhancer-binding protein homologous protein (CHOP) decreases bone formation and causes osteopenia

Pereira

Stadmeyer

Smith

et al. 2007

Bone

View full text Add to dashboard Cite

CCAAT enhancer binding protein (C/EBP) homologous protein (CHOP), is a member of the C/EBP family of nuclear proteins and plays a role in osteoblastic and adipocytic cell differentiation. CHOP is necessary for normal bone formation, but the consequences of its overexpression in vivo are not known. To investigate the direct actions of CHOP on bone remodeling in vivo, we generated transgenic mice overexpressing CHOP under the control of the human osteocalcin promoter. CHOP transgenics exhibited normal weight and reduced bone mineral density. Static and dynamic femoral bone histomorphometry revealed that CHOP overexpression caused reduced trabecular bone volume, secondary to decreased bone formation rates. One of 2 lines displayed a decrease in the number of osteoblasts, but in vivo bromodeoxyuridine labeling demonstrated that CHOP overexpression did not have an effect on osteoblastic cell replication. The decreased osteoblast cell number was accounted by an increase in apoptosis, as determined by DNA fragmentation measured by transferase-mediated digoxigenin-deoxyuridine triphosphate (dUTP) in situ nick-end labeling (TUNEL) reaction. In conclusion, transgenic mice overexpressing CHOP in the bone microenvironment have impaired osteoblastic function leading to osteopenia.

show abstract

Recruitment and Proliferative Responses of Osteoblasts After Mechanical Loading In Vivo Determined Using Sustained-Release Bromodeoxyuridine

Cited by 106 publications

References 14 publications

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation

CCAAT/Enhancer-binding protein homologous protein (CHOP) decreases bone formation and causes osteopenia

Contact Info

Product

Resources

About