Biomedical subjects

Scott D Boden

Publications and source records attributed to Scott D Boden.

40 records · Page 3Linked to original sources

PubMed2002

Osteoinductive molecules in orthopaedics: basic science and preclinical studies.

Osteoinductive molecules are characterized by their ability to promote the formation of bone. Most osteoinductive molecules are cytokines, which are extracellular proteins or peptides that mediate cell to cell signaling. Examples of osteoinductive cytokines are certain bone morphogenetic proteins and some growth and differentiation factors. Some osteoinductive molecules are not secreted molecules. LIM mineralization protein-1 is an example of an intracellular osteoinductive molecule. Significant advances have been made in characterizing the molecular composition and mechanism of action of these osteoinductive molecules. Preclinical studies with these molecules have provided better understanding of the doses, formulation, and delivery mechanism necessary for effective bone formation in model systems of spinal fusion and other orthopaedic problems. The current authors will review the most important basic science and preclinical studies involving these osteoinductive molecules.

Animals↗

PubMed2002

Overexpressed LIM mineralization proteins do not require LIM domains to induce bone.

Rat LIM mineralization protein 1 (LMP-1, an LIM domain protein) mediates bone morphogenetic protein 6 (BMP-6) induction of bone nodule formation in fetal rat calvarial osteoblast (ROB) cultures. We have isolated the complementary DNA (cDNA) for the human homologue of LMP-1 from an adult human heart cDNA library and showed that when overexpressed it is osteoinductive in the same culture system. The recently revised cDNA sequence of Enigma, the protein product of which binds to the insulin receptor and the tyrosine kinase receptor ret, now matches the nucleotide sequence of human LMP-1 (hLMP-1). A truncated, 223 amino acid (AA) LMP-1(t) protein has identical effects as the full-length protein, despite the deletion of the LIM domains. Two splice variants of human LMP-1 have been detected. Human LMP-2 has a 119-base pair (bp) deletion between bp 325 and 444 and a 17-bp insertion at bp 444. The resulting derived protein contains 423 AA with the LIM domains intact and does not induce bone formation when overexpressed in ROB cultures. Human LMP-3 has the same 17 nucleotide insertion at bp 444, resulting in a shift in the reading frame that causes a stop codon to occur at bp 505-507. The resulting 153 AA protein does not have the LIM domains, but overexpression of hLMP-3 induces bone formation in osteoblast cultures. These findings suggest that the LIM domains are not required for LMPs to induce bone formation. In addition, a small region (36 AA) of the LMP-1 protein may be required for bone formation.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

The effects of doxorubicin (adriamycin) on spinal fusion: an experimental model of posterolateral lumbar spinal arthrodesis.

BACKGROUND CONTEXT: Malignant spinal lesions may require surgical excision and segmental stabilization. The decision to perform a concomitant fusion procedure is influenced in part by the need for adjunctive chemotherapy as well as the patient's anticipated survival. Although some evidence exists that suggests that chemotherapy may inhibit bony healing, no information exists regarding the effect of chemotherapy on spinal fusion healing. PURPOSE: To determine the effect of a frequently used chemotherapeutic agent, doxorubicin, on posterolateral spinal fusion rates. STUDY DESIGN/SETTING: Prospective animal model of posterolateral lumbar fusion. OUTCOME MEASURES: Determination of spinal fusion by manual palpation of excised spines. Plain radiographic evaluation of denuded spines to evaluate intertransverse bone formation. METHODS: Thirty-two New Zealand White rabbits underwent posterior intertransverse process fusion at L5-L6 with the use of iliac autograft bone. Rabbits randomly received either intravenous doxorubicin (2.5 mg/kg) by means of the central vein of the ear at the time of surgery (16 animals) or no treatment (16 animals; the control group). The animals were euthanized at 5 weeks, and the lumbar spines were excised. Spine fusion was assessed by manually palpating (by observers blinded to the treatment group) at the level of arthrodesis, and at the adjacent levels proximal and distal. This provided similar information to surgical fusion assessment by palpation in humans. Fusion was defined as the absence of palpable motion. Posteroanterior radiographs of the excised spines were graded in a blinded fashion using a five-point scoring system (0 to 4) devised to describe the amount of bone observed between the L5-L6 transverse processes. Power analysis conducted before initiation of the study indicated that an allocation of 16 animals to each group would permit detection of at least a 20% difference in fusion rates with statistical significance at p=.05. RESULTS: Eleven of the 16 spines (69%) in the control group and 6 of the 16 spines (38%) in the doxorubicin group fused. This difference was statistically significant (=.038). There was no significant correlation (p>.05) between the radiographic grade of bone formation (0 to 4) and fusion as determined by palpation. There were four wound infections in the control group and four in the doxorubicin group. However, solid fusions were palpated in three of these four spines in both the control and treatment groups. CONCLUSIONS: No significant differences in wound complications were noted with doxorubicin administration. A single dose of doxorubicin administered intravenously at the time of surgery appears to play a significant inhibitory role in the process of spinal fusion. If similar effects occur in humans, these data suggest that doxorubicin may be harmful to bone healing in a spine fusion if given during the perioperative period. Further investigation will be necessary to determine the effect of time to aid at determining whether doxorubicin administered several weeks pre- or postoperatively results in improved fusion rate, and whether bone morphogenetic proteins can overcome these inhibitory effects.

Animals↗

PubMedDate not supplied

The ABCs of BMPs.

Bone morphogenetic proteins (BMP) are being increasingly used in orthopaedic surgery. These small molecules are capable of inducing bone formation when delivered in the appropriate concentration and on the appropriate scaffold. Not all BMPs are equally effective, and there are currently only two Food and Drug Administration (FDA)-approved "on-label" applications. There are potential complications related to off-label use of BMPs that need to be understood. When used properly, these molecules have the potential to eliminate the need for iliac crest bone graft harvest and improve the speed and success of bone healing.

Bone Morphogenetic Protein 2↗