A tumor necrosis factor receptor loop peptide mimic inhibits bone destruction to the same extent as anti–tumor necrosis factor monoclonal antibody in murine collagen‐induced arthritis

Abstract

Objective. The cyclic peptide WP9QY (YCWSQYLCY) was designed to mimic the most critical tumor necrosis factor ␣ (TNF␣) recognition loop on TNF receptor I, and it prevents interactions of TNF␣ with its receptor. We undertook this study to compare the effects of the WP9QY peptide on collagen-induced arthritis (CIA) in mice with those of anti-TNF␣ monoclonal antibody.Methods. CIA was induced by primary and secondary immunizations. Osmotic minipumps were implanted in the backs of all mice on the day of the booster injection (day 21), and vehicle, anti-TNF antibody (4 mg/kg/day), or WP9QY peptide (2 mg/kg/day or 4 mg/kg/day) was continuously infused until the mice were killed (day 40). Thereafter, clinical, radiographic, and histologic assessments were performed.Results. WP9QY treatment inhibited CIAinduced increases in the arthritis score, but onset of disease was not delayed by the peptide. The inhibitory effect of WP9QY on inflammation was definitely weaker than that of anti-TNF antibody. Microfocal computed tomography analyses, however, revealed that WP9QY blocked CIA-induced bone destruction at the knee joints to the same extent as did anti-TNF antibody. In addition, WP9QY inhibited synovial pannus infiltration and reduced osteoclast number. Furthermore, inhibition of CIA-induced systemic bone loss by WP9QY was more apparent than that by anti-TNF antibody.Conclusion. The TNF␣ antagonist WP9QY would be a useful template for the development of small molecular inhibitors to prevent both inflammatory bone destruction and systemic bone loss in rheumatoid arthritis.

Potential for estimation of Young's modulus based on computed tomography numbers in bone: A validation study using a nano-indentation test on murine maxilla

“…Previous data obtained from conventional three-point or four-point bending methods cannot be compared with the results of this study. Those test methods were used to measure the bulk bone, including the porous structure, resulting in a modulus approximately five times lower than the results obtained by NI [20,41].…”

“…For this study, 17-week-old male C57BL/6J mice (SLC, Tokyo, Japan) (n=9) were maintained in our animal care facility, as previously described [20]. Nine mice were anesthetized with medetomidine hydrochloride (0.7 mg/kg, Domitor; Zenoaq, Fukushima, Japan) and ketamine hydrochloride (50 mg/kg, Ketalar; Sankyo, Tokyo, Japan), and the mice were sacrificed by cervical dislocation.…”

Peptide drugs accelerate BMP‐2‐induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling

“…The mice were maintained under normal conditions as previously described 27. All of the experimental procedures were reviewed and approved by the Animal Care and Use Committee and Recombination DNA Advisory Committee of Tokyo Medical and Dental University (Tokyo, Japan; authorization numbers: 0140070C, 0150203C2, 0160182A).…”

Increased bone mass in adult prostacyclin-deficient mice

“…Trabecular and cortical regions of long bones were assessed by conducting a longitudinal study with dual X-ray absorptiometry (DXA; DCS-600R; Aloka, Tokyo, Japan; Saito et al 2007, Hussain Mian et al 2008, Alles et al 2009) and determining the trabecular bone volume/tissue volume (%) (BV/TV) by microfocal CT (micro-CT; SMX-90CT, Shimadzu, Kyoto, Japan) respectively. Trabecular bone in secondary spongiosa was measured at a 450-500 mm distance from the growth plate of the tibia to avoid primary spongiosa.…”

“…After micro-CT analysis, the bone specimens were embedded as undecalcified sections in mixtures of methyl methacrylate and 2-hydroxyethylmethacrylate resins, as described previously (Saito et al 2007). Polymerization was performed at 4 8C.…”