Temporal and spatial CGRP innervation in recombinant human bone morphogenetic protein induced spinal fusion in rabbits.
METHODS
Animal experiment using a rabbit posterolateral intertransverse process fusion model.


OBJECTIVE
To explore the temporal and spatial distribution of sensory nerve fibers expressing calcitonin-gene related peptide (CGRP) during spinal fusion induced by recombinant human bone morphogenetic protein-4 and the role of the CGRP innervation in ectopic bone formation and remodeling.


BACKGROUND
Sensory neuropeptide CGRP involved in local bone turnover has been evidenced but its underlying mechanism is poorly understood. Knowledge in the CGRP innervation in ectopic bone induced by bone morphogenetic proteins can help us to understand its role in bone turnover.


METHODS
Twenty-seven New Zealand white rabbits underwent single level posterolateral intertransverse process fusion of the lumbar vertebrae with implantation of porous poly-d,l-lactic acid blocks loaded with 1.25 microg recombinant human bone morphogenetic protein-4 solution. Animals were killed and the operated lumbar vertebrae were harvested for histomorphological evaluation at 3 days (n = 3), 1 week (n = 6), 3 weeks (n = 6), 7 weeks (n = 6), and 12 weeks (n = 6) following surgery, respectively.


RESULTS
New cartilage presented at 1 week postimplantation adjacent to the implant, reached a peak volume at week 3 followed by a drop till week 12 after its ossification. Trabeculae-like woven bone structure presented at week 3. CGRP-positive nerve fibers regenerated already at 3 days postimplantation, reached its peak density at week 3. The CGRP-positive fibers presented both in fibrous tissues adjacent to proliferating cartilages and in bone marrow of newly formed trabecular bone.


CONCLUSIONS
The observed spatial and temporal regeneration of CGRP-positive nerve fibers in ectopic bone formation suggested CGRP innervation is associated with ectopic osteogenesis.
Wang
Xiao-Yun
XY
Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
Guo
Xia
X
Qu
Shu-Xin
SX
Weng
Jie
J
Cheng
Chung-Yiu Jack
CY
D000818:Animals; D055395:Bone Morphogenetic Protein 1 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology; D002828:Choristoma / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000627:therapeutic use; D008159:Lumbar Vertebrae / Q000294:innervation / Q000503:physiopathology / Q000601:surgery; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000627:therapeutic use; D011183:Postoperative Complications / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000009:adverse effects; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013123:Spinal Fusion / Q000379:methods*; D013131:Spine / Q000294:innervation / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors
D011091:Polyesters; D011108:Polymers; D011993:Recombinant Fusion Proteins; D019344:Lactic Acid; C033616:poly(lactide); C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1; D015740:Calcitonin Gene-Related Peptide