NELL-1 injection maintains long-bone quantity and quality in an ovariectomy-induced osteoporotic senile rat model.
Over 10 million Americans have osteoporosis, and is the predominant cause of fractures in the elderly. Treatment of fractures in the setting of osteoporosis is complicated by a suboptimal bone regenerative response due to a decline in the number of osteoblasts, their function, and survival. Consequently, an osteogenic therapeutic to prevent and treat fractures in patients with osteoporosis is needed. Nel-like molecule-1 (NELL-1), a novel osteoinductive growth factor, has been shown to promote bone regeneration. In this study, we aim to demonstrate the capacity of recombinant NELL-1 to prevent ovariectomy (OVX)-induced osteoporosis in a senile rat model. Ten-month-old female Sprague-Dawley rats underwent either sham surgery or OVX. Subsequently, 50 μL of 600 μg/mL NELL-1 lyophilized onto a 0-50-μm tricalcium phosphate (TCP) carrier was injected into the femoral bone marrow cavity while phosphate-buffered saline (PBS) control was injected into the contralateral femur. Our microcomputed tomography results showed that OVX+PBS/TCP control femurs showed a continuous decrease in the bone volume (BV) and bone mineral density (BMD) from 2 to 8 weeks post-OVX. In contrast, OVX+NELL-1/TCP femurs showed resistance to OVX-induced bone resorption showing BV and BMD levels similar to that of SHAM femurs at 8 weeks post-OVX. Histology showed increased endosteal-woven bone, as well as decreased adipocytes in the bone marrow of NELL-1-treated femurs compared to control. NELL-1-treated femurs also showed increased immunostaining for bone differentiation markers osteopontin and osteocalcin. These findings were validated in vitro, in which addition of NELL-1 in OVX bone marrow stem cells resulted in increased osteogenic differentiation. Thus, NELL-1 effectively enhances in situ osteogenesis in the bone marrow, making it potentially useful in the prevention and treatment of osteoporotic fractures.
Section of Orthodontics School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095, USA.
Jinny
J
Kwak
Janette N
JN
Zara
Michael
M
Chiang
Richard
R
Ngo
Jia
J
Shen
Aaron W
AW
James
Khoi M
KM
Le
Crystal
C
Moon
Xinli
X
Zhang
Zhongru
Z
Gou
Kang
K
Ting
Chia
C
Soo
D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000008:administration & dosage*; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
C484480:Nell1 protein, rat; D009419:Nerve Tissue Proteins