Platelet-derived growth factor enhances bone cell replication, but not differentiated function of osteoblasts

Area of Science:

• Bone Biology
• Cell Signaling
• Regenerative Medicine

Background:

• Platelet-derived growth factor (PDGF) is a mitogen existing as PDGF-AA and PDGF-BB dimers.
• PDGF-BB is prevalent in circulation, while PDGF-AA is secreted by normal bone cells.
• Previous studies showed PDGF-BB inconsistently affects collagen synthesis in fetal rat calvariae.

Purpose of the Study:

• To investigate the cellular localization and effects of PDGF-AA and PDGF-BB on fetal rat calvariae.
• To assess PDGF's impact on bone cell replication, matrix formation, and osteoclast activity.

Main Methods:

• Cultured 21-day-old fetal rat calvariae with human recombinant PDGF-AA and -BB (0.03-3.3 nM).
• Assessed cell replication using histomorphometry and autoradiography with [3H]thymidine incorporation.
• Measured collagen synthesis and bone matrix formation biochemically and histologically.

Main Results:

• Both PDGF-AA and -BB significantly increased DNA synthesis (1.5-3 fold), with PDGF-BB being more potent.
• PDGF preferentially stimulated fibroblast replication in the periosteum, increasing labeling index by 3-fold (AA) and 5-fold (BB).
• PDGF treatment inhibited bone matrix formation, increased osteoclast numbers (2-3 fold), and eroded surface, with no evidence of osteoblast differentiation.

Conclusions:

• PDGF-AA and -BB act as mitogens on multiple bone cells, including osteoblasts and osteoclasts.
• PDGF treatment disrupts and inhibits bone matrix formation in fetal rat calvariae.
• The primary effect of PDGF in this model is selective stimulation of fibroblast replication and function.