The regeneration of bone is a remarkable, complex physiological process,
and BMPs are a formidable clinical tool to promote its regeneration.
By defining roles played by BMPs in developmental biology and bone
regeneration, significant progress has been made to identify cell-signaling
molecules and their regulators. For example, the regulators of BMPs
that include noggin, chordin, cerberus, dan, and gremlin may be harnessed
as therapies to offset calcification encountered after total hip
arthroplasties. Furthermore, exploiting BMPs and Smads may generate
new therapeutic options for bone repair. Another compelling clinical
consideration is the trans-acting factor osteoblast-specific factor-2,
which can promote osteoblast differentiation. Moreover, the affiliation
of osteoblast-specific factor-2 with heritable disorders merits exploration.
A recognized daunting challenge includes a carrier/delivery system
for the powerful morphogenetic therapeutic tools, as well as osteoprogenitor
cells and intracellular transduction and transcriptional factors.
In addition, the long-term effects of administering superphysiological
doses of rhBMPs to patients must be assessed systematically. A new
generation carrier/delivery system may be the answer to offset dosing
liabilities as well as to provide residence for exogenous, BMP-receptive
osteoprogenitor cells (111,112). The areas highlighted in this review
offer fertile territory for thought and research to develop rational
clinical treatments to promote bone regeneration and to understand
some of the biological roles of BMPs.