TGFbeta3 and loading increases osteocyte survival in human cancellous bone cultured ex vivo.

The goal of this study was to assess the effect of the addition of TGFbeta(3), alone or in combination with loading, on the survival of osteocytes in 3D human explant cancellous bone during long-term culture in an ex vivo loading bioreactor. Human cancellous bone explants were cultured for up to 14 days with or without TGFbeta(3) (15 ng ml(-1)) and with or without loading (300 cycles, at 1 Hz, producing 4000 microstrain). Bone core response was visualized using undecalcified histology with morphological methods after embedding with Technovit 9100 New resin.

Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localized bone destruction.

Introduction: Osteocyte apoptosis co-localizes with sites of osteoclastic bone resorption in vivo, but to date, no causal molecular or signaling link has been identified between these two processes.

Materials And Methods: Osteocyte apoptotic bodies (OABs) derived from the MLO-Y4 osteocyte-like cell line and primary murine osteocytes and apoptotic bodies (ABs) derived from primary murine osteoblasts were introduced onto the right parietal bone of murine calvariae, and osteoclastic bone resorption was examined 5 days after treatment. In addition, the ability of primary murine and cell line-derived OABs to support osteoclastogenesis was examined in vitro in co-culture with murine bone marrow hematopoietic progenitors in the absence of RANKL or macrophage-colony stimulating factor.

The osteocyte lineage.

The osteocyte resides in the lacuna/canalicular system in bone and has been hypothesized to orchestrate local bone remodeling. Certainly the identification of the osteocyte as the source of Sclerostin, a molecule that regulates osteoblast function, has supported this possibility. As our understanding of this cell increases it has become clear that it has more far reaching influence than simply local bone turnover activity.

The biology of osteocytes.

Osteocytes, the most abundant cell type in bone, remain the least characterized. Several theories have been proposed regarding their function, including osteolysis, sensing the strains produced in response to mechanical loading of bones, and producing signals that affect the function of osteoblasts and osteoclasts and hence, bone turnover. This review also discusses the role of osteocyte apoptosis in targeted bone remodeling and proposes that the occurrence of osteocyte apoptosis is consistent with the description of apoptosis as an essential homeostatic mechanism for the healthy maintenance of tissues.

Physiologic oxygen enhances human embryonic stem cell clonal recovery and reduces chromosomal abnormalities.

Human embryonic stem cells (hESC) have great potential in regenerative medicine, provided that culture systems are established that maintain genomic integrity. Here we describe a comparison of the effects of culture in either physiologic oxygen (2%) or room oxygen (21%) on the hESC lines, H1, H9, and RH1. Physiologic oxygen enabled an average sixfold increase in clone recovery across the hESC lines tested (p < 0.

Compartmentalized megakaryocyte death generates functional platelets committed to caspase-independent death.

Caspase-directed apoptosis usually fragments cells, releasing nonfunctional, prothrombogenic, membrane-bound apoptotic bodies marked for rapid engulfment by macrophages. Blood platelets are functional anucleate cells generated by specialized fragmentation of their progenitors, megakaryocytes (MKs), but committed to a constitutive caspase-independent death. Constitutive formation of the proplatelet-bearing MK was recently reported to be caspase-dependent, apparently involving mitochondrial release of cytochrome c, a known pro-apoptogenic factor.

Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone.

Bone is removed or replaced in defined locations by targeting osteoclasts and osteoblasts in response to its local history of mechanical loading. There is increasing evidence that osteocytes modulate this targeting by their apoptosis, which is associated with locally increased bone resorption. To investigate the role of osteocytes in the control of loading-related modeling or remodeling, we studied the effects on osteocyte viability of short periods of mechanical loading applied to the ulnae of rats.