Immune and inflammatory pathways are involved in inherent bone marrow ossification.
BACKGROUND
Bone marrow plays a key role in bone formation and healing. Although a subset of marrow explants ossifies in vitro without excipient osteoinductive factors, some explants do not undergo ossification. The disparity of outcome suggests a significant heterogeneity in marrow tissue in terms of its capacity to undergo osteogenesis.


OBJECTIVE
We sought to identify: (1) proteins and signaling pathways associated with osteogenesis by contrasting the proteomes of ossified and poorly ossified marrow explants; and (2) temporal changes in proteome and signaling pathways of marrow ossification in the early and late phases of bone formation.


METHODS
Explants of marrow were cultured. Media conditioned by ossified (n = 4) and poorly ossified (n = 4) subsets were collected and proteins unique to each group were identified by proteomic analysis. Proteomic data were processed to assess proteins specific to the early phase (Days 1-14) and late phase (Days 15-28) of the culture period. Pathways involved in bone marrow ossification were identified through bioinformatics.


RESULTS
Twenty-eight proteins were unique to ossified samples and eight were unique to poorly ossified ones. Twelve proteins were expressed during the early phase and 15 proteins were specific to the late phase. Several identified pathways corroborated those reported for bone formation in the literature. Immune and inflammatory pathways were specific to ossified samples.


CONCLUSIONS
The marrow explant model indicates the inflammatory and immune pathways to be an integral part of the osteogenesis process.
Harvard-MIT Division of Health Sciences and Technology, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, PRB 252, Cambridge, MA 02139, USA. ugurkan@rics.bwh.harvard.edu
Umut Atakan
UA
Gurkan
Ryan
R
Golden
Vipuil
V
Kishore
Catherine P
CP
Riley
Jiri
J
Adamec
Ozan
O
Akkus
D000818:Animals; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology*; D019295:Computational Biology; D017077:Culture Media, Conditioned / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D009999:Ossification, Heterotopic; D010012:Osteogenesis; D040901:Proteomics / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction; D013997:Time Factors; D046509:Tissue Culture Techniques; D055114:X-Ray Microtomography
D017077:Culture Media, Conditioned; D018836:Inflammation Mediators