title: Nell-1 induced bone formation within the distracted intermaxillary suture.
abstract: Maxillary bone deficiencies, such as cleft palate and underdeveloped maxilla that require bone graft or regeneration after orthopedic or surgical expansion, pose a significant biomedical burden. Nell-1 is a secreted molecule that possesses chordin-like domains and induces cranial suture bone growth and osteoblast differentiation. To accelerate bone formation in acutely distracted palatal sutures, rat organ cultures were stimulated with Nell-1 or BMP-7 for 8 days in vitro. We hypothesized that Nell-1 stimulation to the distracted palatal suture would accelerate bone formation. Distracted palates of 4-week-old male rats were maintained in an organ culture system, and tissue was either unstimulated or stimulated with Nell-1 or BMP-7 for 8 days. MicroCT was conducted to quantitate bone formation, while alcian blue staining was conducted for cartilage localization. Immunohistochemistry of Sox9 for chondrocyte proliferation, type X collagen for hypertrophic cartilage in endochondral bone formation, and bone sialoprotein for bone formation was conducted to characterize the cellular mechanism of newly developed tissues. Distracted palates cultured in the presence of Nell-1 or BMP-7 produced statistically significantly (P < 0.05) more bone and cartilage within the intermaxillary suture, relative to unstimulated control samples. While both BMP-7 and Nell-1 induced similar bone formation in the distracted suture, BMP-7 induced both chondrocyte proliferation and differentiation, while Nell-1 accelerated chondrocyte hypertrophy and endochondral bone formation. While both Nell-1 and BMP-7 are effective in forming bone in the distracted palatal suture, they are suggested to have distinctively different mechanisms. The ability of Nell-1 to accelerate bone formation within the palate suture demonstrates the versatility of Nell-1 within the craniofacial complex as well as an exciting advance in palate suture defect healing.
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA 90095, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Cowan
authors.forename: Samson
authors.initials: S
authors.lastname: Cheng
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
authors.forename: Benjamin
authors.initials: B
authors.lastname: Walder
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wu
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002356:Cartilage / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D003393:Cranial Sutures / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000601:surgery; D008297:Male; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010012:Osteogenesis; D010159:Palate / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C484480:Nell1 protein, rat; D009419:Nerve Tissue Proteins; D016212:Transforming Growth Factor beta