BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing

Abstract

Adult bones have a notable regenerative capacity. Over 40 years ago, an intrinsic activity capable of initiating this reparative response was found to reside within bone itself, and the term bone morphogenetic protein (BMP) was coined to describe the molecules responsible for it. A family of BMP proteins was subsequently identified, but no individual BMP has been shown to be the initiator of the endogenous bone repair response. Here we demonstrate that BMP2 is a necessary component of the signaling cascade that governs fracture repair. Mice lacking the ability to produce BMP2 in their limb bones have spontaneous fractures that do not resolve with time. In fact, in bones lacking BMP2, the earliest steps of fracture healing seem to be blocked. Although other osteogenic stimuli are still present in the limb skeleton of BMP2-deficient mice, they cannot compensate for the absence of BMP2. Collectively, our results identify BMP2 as an endogenous mediator necessary for fracture repair.

Autogenous regulation of a network of bone morphogenetic proteins (BMPs) mediates the osteogenic differentiation in murine marrow stromal cells

“…More germane to the observations and conclusions that we have drawn from our studies was the demonstration that bones lacking BMP2 showed that the earliest steps of fracture healing seem to be blocked. These results lead these authors to the central conclusion that although other osteogenic stimuli were still present in the limb skeleton of these BMP2-deficient mice, that they cannot compensate for the absence of BMP2 [30].…”

Molecular profiling of synovial joints: Use of microarray analysis to identify factors that direct the development of the knee and elbow

“…The plasmid used for generating the Tbx4 probe was a gift of Dr. V. Papaioannou (Columbia University, New York, NY); Rspo2, Dr. J. Yoon (Maine Medical Center, Portland, ME). Probes for Col2a1, Hoxc10, and Tgfbi were generated as previously described (Storm and Kingsley, 1996;Ferguson et al, 2003;Choe et al, 2006;Tsuji et al, 2006). Probe for Sfrp2 was generated using the following primers 5 0 -ACATTCCCAGTGGT CTCTTGT-3 0 .…”

Botulinum Toxin-induced Muscle Paralysis Inhibits Heterotopic Bone Formation

“…Given the known mechanism of action of BTxA (inhibition of neurotransmitter release), we therefore speculated that the blockade of neuromuscular signaling by BTxA inhibits neuromuscular interactions integral to the osteogenic response elicited by musculoskeletal trauma. Furthermore, because fracture healing and HO share common initiating events (including inflammation and BMP signaling) [17,27,30,32], we also speculated that BTxA-induced muscle paralysis would prevent the formation of heterotopic bone. However, interpreting the precise mechanism by which muscle paralysis inhibits osteogenesis in the rat fracture model is confounded by the heterogeneity of the tissue response, soft tissue injury, and modified gait kinematics, all of which can alter the observed cellular responses.…”