Tag Archives: abstract

Minocycline Inhhibits Osteoclastogenesis in Mouse Cells

Abstract

Inhibitory effect of minocycline on osteoclastogenesis in mouse bone marrow cells.

To study the effects of minocycline hydrochloride (MINO) on the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive multinucleated osteoclast-like cells in mouse bone marrow cells (BMCs) treated with 1α,25(OH)(2)D(3) or soluble receptor activator of nuclear factor-κB ligand (s-RANKL).
Mouse BMCs were cultured in alpha-modified minimum essential medium containing foetal calf serum (10%) and tetracyclines (2.5, 5 and 10μM), such as MINO, tetracycline hydrochloride (TC), oxytetracycline hydrochloride (OXT) or doxycycline (DOXY) in the presence of 1α,25(OH)(2)D(3) (10nM) or s-RANKL (20ng/ml) for 7 days, and the number of TRAP staining-positive osteoclast-like cells was counted. In RNA isolated from BMCs treated with 1α,25(OH)(2)D(3) or s-RANKL in the presence or absence of MINO, the expressions of osteoclast differentiation relating to mRNA were analysed by reverse transcription-polymerase chain reaction. Cell viability was examined in mouse BMCs and rabbit osteoclasts treated with MINO (0.25-20μM and 2-50μM, respectively) for 24h.
MINO, TC, OXT or DOXY inhibited 1α,25(OH)(2)D(3)-induced osteoclast-like cell formation in mouse BMCs dose dependently. MINO suppressed 1α,25(OH)(2)D(3)-induced up-regulation of mRNA expressions of TRAP, cathepsin K, carbonic anhydrase II, and calcitonin receptor, but not RANKL. MINO inhibited s-RANKL-induced osteoclast-like cell formation and up-regulation of mRNA expressions for nuclear factor of activated T-cells c1 (NFATc1), a key regulator of osteoclast differentiation; however, MINO had no effects on the viability of mouse BMCs and rabbit osteoclasts.
MINO inhibits RANKL-induced osteoclastogenesis via down-regulation of NFATc1 mRNA expression in osteoclast precursor cells.

Nagasawa T, Arai M, Togari A
Arch. Oral Biol. Sep 2011
PMID: 21377143

Minocycline Stimulates Bone Formation in Ovariectomized Rats

Abstract

Effect of minocycline on osteoporosis.

The effect of oral minocycline on osteopenia in ovariectomized (OVX) old rats was examined in this study. Rats were divided into 4 groups: sham-operated, OVX followed by treatment with vehicle, minocycline, or 17 beta-estradiol. The treatment was initiated one day after OVX and proceeded for 8 wks. OVX reduced bone mineral density (BMD) in the whole femur and in the femoral regions that are enriched in trabecular bone. Treatment with minocycline or estrogen prevented a decrease in BMD. Femoral trabecular bone area, trabecular number, and trabecular thickness were reduced, and trabecular separation was increased by OVX. Treatment with minocycline or estrogen abolished the detrimental effects induced by OVX. OVX also reduced indices that reflect the interconnectivity of trabecular bone, and the loss of trabecular connectivity was prevented by treatment with minocycline or estrogen. Based on the levels of urinary pyridinoline, we showed that the effect of estrogen, but not minocycline, was primarily through its inhibitory effect on bone resorption. Analysis of bone turnover activity suggests that OVX increased parameters associated with bone resorption (eroded surface) and formation (osteoid surface, mineralizing surface, mineral apposition rate, and bone formation rate). Treatment with minocycline reduced bone resorption modestly and stimulated bone formation substantially. In contrast, treatment with estrogen drastically reduced parameters associated with both bone resorption and formation. We have concluded that oral minocycline can effectively prevent the decrease in BMD and trabecular bone through its dual effects on bone resorption and formation.

Williams S, Wakisaka A, Zeng QQ, Barnes J…
Adv. Dent. Res. Nov 1998
PMID: 9972125

Palash Prevents Bone Loss and Stimulates Formation in Ovariectomized Rats

Abstract

Total extract and standardized fraction from the stem bark of Butea monosperma have osteoprotective action: evidence for the nonestrogenic osteogenic effect of the standardized fraction.

The aim of this study was to determine the skeletal effects of Butea total extract (BTE) and its acetone soluble fraction (ASF) from Butea monosperma, which is rich in methoxyisoflavones, in ovariectomized (OVx) rats, a model for postmenopausal bone loss.
BTE (1.0 g kg d) and ASF (100 mg kg d) were given orally for 12 weeks to adult OVx rats. The sham-operated and ovariectomy + vehicle groups served as controls. Bone mineral density, osteoid formation (mineral apposition rate and bone formation rate), bone microarchitecture, and bone turnover/resorption markers were studied. Phytoestrogens in rats given BTE and ASF were analyzed by high-performance liquid chromatography. One-way analysis of variance was used to test significance of effects.
OVx rats treated with either BTE or ASF exhibited increased bone mineral density in trabecular bones and improved trabecular microarchitecture compared with the ovariectomy + vehicle group. ASF treatment was more efficient than BTE treatment in maintaining trabecular microarchitecture. Serum osteocalcin and urinary type 1 collagen levels in OVx rats treated with either BTE or ASF were significantly lower than those of the ovariectomy + vehicle group. ASF treatment led to increased mineral apposition rate and bone formation rate compared with ovariectomy + vehicle, whereas BTE had no such effect. In the uterotropic assay, BTE was mildly estrogenic in adult OVx rats. In immature rats, BTE exhibited both estrogenicity and antiestrogenicity. ASF had neither uterine estrogenicity nor antiestrogenicity. Analysis of phytoestrogens revealed significant enrichment of cladrin, isoformononetin, and medicarpin in ASF over BTE.
Derived from B monosperma, ASF at a 10-fold lower dose than that of BTE was effective in preventing OVx-induced bone loss and stimulated new-bone formation.

Pandey R, Gautam AK, Bhargavan B, Trivedi R…
Menopause
PMID: 20395887

Palash Reduces Bone Loss in Ovariectomized Rats

Abstract

Greater Skeletal Gains in Ovary Intact Rats at Maturity Are Achieved by Supplementing a Standardized Extract of Butea monosperma Stem Bark that Confers Better Bone Conserving Effect following Ovariectomy and Concurrent Treatment Withdrawal.

With a longitudinally designed study, we tested whether an acetone soluble fraction (ASF) from the stem bark of Butea monosperma resulted in maximizing bone gain in rats during growth and maturation and thus protected against osteopenia following ovariectomy (OVx) with concomitant treatment withdrawal. Female rats at weaning were given ASF (100 mg/kg/d) or vehicle for 12 weeks, and baseline skeletal parameters (micro-CT) and total plasma antioxidant status (TAS) were measured. At this stage, one group was OVx and the other group was sham operated. Vehicle group (untreated) after OVx was given E2 or continued with vehicle (OVx control). ASF group after OVx was given vehicle (ASF withdrawn, ASFW). After another 12 weeks, all groups were killed and various skeletal parameters were determined. ASF resulted in substantially better skeletal parameters and higher plasma TAS over control at maturity. Rats treated with ASF before OVx had reduced rates of bone loss compared to OVx control. Twelve weeks after OVx, the ASFW group exhibited better trabecular microarchitectural preservation, bone turnover profiles, increased cortical deposition, and biomechanical strength over the OVx control, and the effects were comparable to OVx + E2 group. ASF supplementation during skeletal growth could maximize bone accrual and could confer increased resistance to post-OVx osteopenia despite treatment withdrawal.

Srivastava K, Khan K, Tyagi AM, Khan MP…
Evid Based Complement Alternat Med 2013
PMID: 23710224 | Free Full Text

O-methoxy substitutions of free phenolic hydroxyl groups of the most abundant soy isoflavones (genistein and daidzein) enhance the lipophilicity, metabolic stability, and uterine safety, thus improving pharmacokinetic/metabolic stability profiles of genistein and daidzein and, consequently, enhance the pharmacodynamic effect (in vivo potency) [12, 13]. In our phytopharmacological evaluation program, aimed at discovering effective alternative strategy for reducing the risk of developing postmenopausal osteopenia, we showed that a standardized fraction (an acetone soluble fraction, ASF) made from the stem bark of Butea monosperma contained four methoxyisoflavones: cajanin (7-methoxy genistein), medicarpin (a methoxypterocarpan with cyclized genistein ring structure), isoformononetin (7-methoxy daidzein), and cladrin (3′4,-dimethoxy daidzein) at percent concentration of 0.061, 0.019, 0.007, and 0.003, respectively [14]. Each one of these, when administered to female rats for four weeks after weaning resulted in increased BMD, bone strength, and bone formation rate with varying efficacy. In vitro, all four compounds stimulated osteoblast function more potently than genistein and daidzein by different modes of action [15–17]. These observations prompted us to hypothesize that the presence of these methoxyisoflavones in the ASF could synergistically augment peak bone mass accrual in female rats at maturity that will confer a superior bone conserving ability after surgical menopause (due to ovariectomy, OVx) even as the treatment is withdrawn.

Minocycline Increases Bone Density in Ovariectomized Rats

Abstract

Treatment of osteoporosis with MMP inhibitors.

In the current study, we examined the effects of minocycline on the osteopenia of ovariectomized (OVX) aged rats using the marrow ablation model. This injury induces rapid bone formation followed by bone resorption in the marrow cavity. Old female rats were randomly divided into five groups: sham, OVX, OVX + minocycline (5-15 mg/day, orally), OVX + 17 beta-estradiol (25 micrograms/day, subcutaneously), and OVX + both agents. Rats were OVX, treated with minocycline and/or estrogen, followed by marrow ablation. Bone samples were collected 16 days post-marrow ablation. X-ray radiography of bones operated on showed that treatment of OVX old rats with minocycline increased bone mass in diaphyseal region. Diaphyseal bone mineral density (BMD) was measured by DEXA scan. Diaphyseal BMD of OVX rats was increased 17-25% by treatment with 5-15 mg of minocycline or 17 beta-estradiol. The effects of minocycline and estrogen treatments on the expression of osteoblast and osteoclast markers were also examined. Northern and dot blot analysis of RNA samples showed that treatment of OVX aged rats with minocycline increased the expression of type I collagen (COL I) (49%) and decreased that of interleukin-6 (IL-6) (31%). In contrast, estrogen treatment decreased the expression of interleukin-6 (IL-6) (39%), carbonic anhydrase II (CA II) (36%), and osteopontin (OP) (37%). Neither minocycline nor 17 beta-estradiol had an effect on the expression of osteocalcin (OC) and alkaline phosphatase (AP). To elucidate the mechanism by which minocycline prevented the loss of bone in OVX aged rats, we examined the colony-formation potential of bone marrow stromal cells in ex vivo cultures. Minocycline stimulated the colony-forming efficiency of marrow stromal cells derived from old animals. We have therefore concluded that the modest increase in BMD noted in OVX aged rats, in response to minocycline treatment, may be due to a change in bone remodeling that favors bone formation; and the anabolic effect of minocycline is likely due to its effect on the expression of COL I and/or the metabolism of osteoprogenitor cells.

Williams S, Barnes J, Wakisaka A, Ogasa H…
Ann. N. Y. Acad. Sci. Jun 1999
PMID: 10415730

Review: Exercises to Reduce Falls, and Improve Gait and Balance

Abstract

Effects of different exercise interventions on risk of falls, gait ability, and balance in physically frail older adults: a systematic review.

The aim of this review was to recommend training strategies that improve the functional capacity in physically frail older adults based on scientific literature, focusing specially in supervised exercise programs that improved muscle strength, fall risk, balance, and gait ability. Scielo, Science Citation Index, MEDLINE, Scopus, Sport Discus, and ScienceDirect databases were searched from 1990 to 2012. Studies must have mentioned the effects of exercise training on at least one of the following four parameters: Incidence of falls, gait, balance, and lower-body strength. Twenty studies that investigated the effects of multi-component exercise training (10), resistance training (6), endurance training (1), and balance training (3) were included in the present revision. Ten trials investigated the effects of exercise on the incidence of falls in elderly with physical frailty. Seven of them have found a fewer falls incidence after physical training when compared with the control group. Eleven trials investigated the effects of exercise intervention on the gait ability. Six of them showed enhancements in the gait ability. Ten trials investigated the effects of exercise intervention on the balance performance and seven of them demonstrated enhanced balance. Thirteen trials investigated the effects of exercise intervention on the muscle strength and nine of them showed increases in the muscle strength. The multi-component exercise intervention composed by strength, endurance and balance training seems to be the best strategy to improve rate of falls, gait ability, balance, and strength performance in physically frail older adults.

Cadore EL, Rodríguez-Mañas L, Sinclair A, Izquierdo M
Rejuvenation Res Apr 2013
PMID: 23327448 | Free Full Text

Virtual Reality Training Improves Balance in Older Adults

Abstract

Effects of balance training using a virtual-reality system in older fallers.

Poor balance is considered a challenging risk factor for falls in older adults. Therefore, innovative interventions for balance improvement in this population are greatly needed. The aim of this study was to evaluate the effect of a new virtual-reality system (the Balance Rehabilitation Unit [BRU]) on balance, falls, and fear of falling in a population of community-dwelling older subjects with a known history of falls. In this study, 60 community-dwelling older subjects were recruited after being diagnosed with poor balance at the Falls and Fractures Clinic, Nepean Hospital (Penrith, NSW, Australia). Subjects were randomly assigned to either the BRU-training or control groups. Both groups received the usual falls prevention care. The BRU-training group attended balance training (two sessions/week for 6 weeks) using an established protocol. Change in balance parameters was assessed in the BRU-training group at the end of their 6-week training program. Both groups were assessed 9 months after their initial assessment (month 0). Adherence to the BRU-training program was 97%. Balance parameters were significantly improved in the BRU-training group (P < 0.01). This effect was also associated with a significant reduction in falls and lower levels of fear of falling (P < 0.01). Some components of balance that were improved by BRU training showed a decline after 9 months post-training. In conclusion, BRU training is an effective and well-accepted intervention to improve balance, increase confidence, and prevent falls in the elderly.

Duque G, Boersma D, Loza-Diaz G, Hassan S…
Clin Interv Aging 2013
PMID: 23467506 | Free Full Text

Hippotherapy for Balance

Abstract

Effects of hippotherapy on mobility, strength and balance in elderly.

To assess the chronic effects of hippotherapy on functional mobility, muscle strength and balance in elderly.
28 volunteers, between the age of 60 and 84, were randomly recruited and divided in experimental group (EG), with 12 individuals (8 women and 4 men) and control group (CG), with 16 individuals (14 women and 2 men). The EG group participated in an 8-week hippotherapy program. Before and after the study period functional mobility was assessed and measured by Time Up and Go Test (TUG), muscle strength of the lower limbs was measured by 30s Chair Stand Test (30CST) and performance in balance was measured by the Berg Balance Scale (BBS). A mixed ANOVA model (group×testing time) was applied to establish the effect of the different groups on the functional variables.
The functional capacity of the EG group was increased if compared to CG group after the intervention of the BBS (p=0.003) and 30CST (p=0.032), but not of the TUG (p=0.063).
The results indicated that hippotherapy improves the lower limb strength and balance in elderly.

de Araújo TB, de Oliveira RJ, Martins WR, de Moura Pereira M…
Arch Gerontol Geriatr
PMID: 23290005

Proprioception Training for Balance

Abstract

Effects of 12-week proprioception training program on postural stability, gait, and balance in older adults: a controlled clinical trial.

The purpose of this study was to evaluate the effect of a 12-week-specific proprioceptive training program on postural stability, gait, balance, and fall prevention in adults older than 65 years. The present study was a controlled clinical trial. Forty-four community dwelling elderly subjects (61-90 years; mean age, 78.07 ± 5.7 years) divided into experimental (n = 20) and control (n = 24) groups. The participants performed the Berg balance test before and after the training program, and we assessed participants’ gait, balance, and the risk of falling, using the Tinetti scale. Medial-lateral plane and anterior-posterior plane displacements of the center of pressure, Sway area, length and speed, and the Romberg quotient about surface, speed, and distance were calculated in static posturography analysis (EPS pressure platform) under 2 conditions: eyes open and eyes closed. After a first clinical evaluation, patients were submitted to 12 weeks proprioception training program, 2 sessions of 50 minutes every week. This program includes 6 exercises with the BOSU and Swiss ball as unstable training tools that were designed to program proprioceptive training. The training program improved postural balance of older adults in mediolateral plane with eyes open (p < 0.05) and anterior-posterior plane with eyes closed (p < 0.01). Significant improvements were observed in Romberg quotient about surface (p < 0.05) and speed (p < 0.01) but not about distance (p > 0.05). After proprioception training, gait (Tinetti), and balance (Berg) test scores improved 14.66% and 11.47% respectively. These results show that 12 weeks proprioception training program in older adults is effective in postural stability, static, and dynamic balance and could lead to an improvement in gait and balance capacity, and to a decrease in the risk of falling in adults aged 65 years and older.

Martínez-Amat A, Hita-Contreras F, Lomas-Vega R, Caballero-Martínez I…
J Strength Cond Res Aug 2013
PMID: 23207891

AGE Consumption Increases Resorption in Rats

Abstract

Effects of model Maillard compounds on bone characteristics and functionality.

BACKGROUND: Physical and biomechanical properties of bone can be affected by non-enzymatic crosslinks, which are implicated in bone pathologies such as osteoporosis. The purpose of this study was to analyse the effects of the consumption of model Maillard reaction product (MRP) from glucose-lysine heated for 90 min at 150 °C (GL90) on bone composition and features. Rats were fed either a control diet or a diet containing 30 g kg(-1) GL90 for 88 days. Food consumption and the animals’ body weights were monitored. After sacrifice, the femur, pelvic bone and tibia were removed for analysis of their composition and physical and biomechanical properties. RESULTS: The organic matrix of the femur and the density of the pelvic bone decreased after MRP intake, whereas pentosidine content increased greatly with respect to the control group (41.7 ± 9.9 vs 171.4 ± 3.3 mmol mol(-1) collagen). The rising level of C-telopeptide degradation products from type I collagen (β-CTX) suggested a possible situation of increased bone resorption and/or higher turnover. CONCLUSION: In conjunction, the detrimental effect on the organic matrix, the situation of higher resorption and/or bone turnover indicated by the β-CTX values and the high pentosidine content in bone provoked negative consequences on certain mechanical properties such as the ability to withstand force and absorb energy without failure.

Roncero-Ramos I, Delgado-Andrade C, Rufián-Henares JA, Carballo J…
J. Sci. Food Agric. Feb 2013
PMID: 23420603