Ciliary neurotrophic factor (CNTF) is produced by astrocytes and promotes neurogenesis and neuroprotection. Little is known about the role of CNTF in affective behavior. We investigated whether CNTF affects depressive- and anxiety-like behavior in adult mice as tested in the forced swim, sucrose preference and elevated-T maze tests. Female wild type CNTF+/+ mice more readily developed behavioral despair with increased immobility time and decreased latency to immobility in the forced swim test than male CNTF+/+ littermates. The lack of CNTF in CNTF-/- mice had an opposite effect on depressive-like behavior in female mice (reduced immobility time and increased sucrose preference) vs. male mice (increased immobility time). Female wildtype mice expressed more CNTF in the amygdala than male mice. Ovariectomy increased CNTF expression, as well as immobility time, which was significantly reduced in CNTF-/- mice, suggesting that CNTF mediates overiectomy-induced immobility time, possibly in the amygdala. Progesterone but not 17-β estradiol inhibited CNTF expression in cultured C6 astroglioma cells. Progesterone treatment also reduced CNTF expression in the amygdala and decreased immobility time in female CNTF+/+ but not in CNTF-/- mice. Castration did not alter CNTF expression in males nor their behavior. Lastly, there were no effects of CNTF on the elevated T-maze, a behavioral test of anxiety, suggesting that a different mechanism may underlie anxiety-like behavior. This study reveals a novel CNTF-mediated mechanism in stress-induced depressive-like behavior and points to opportunities for sex-specific treatments for depression, e.g. progesterone in females and CNTF-stimulating drugs in males.

The purpose of this study is to characterize the compact bone remodeling of the ovariectomized ewe and its effectiveness as an animal model for studies of postmenopausal osteoporosis. The use of animal models is a beneficial way to evaluate the effectiveness of medical devices and therapeutic agents for treating diseases. The ovine model is an attractive option because of its large size and similar bone remodeling to humans. However, this species, like most animals, does not undergo a natural menopause, making an ovariectomy necessary for studies of estrogen depletion. The OVX (ovariectomized) sheep has been widely accepted as a model for loss of BMD. However, even with its advantages seasonality has been shown to have an effect on the bone remodeling in the ovine model. Thus, this study focused on characterizing the seasonal and anatomical variation in the compact bone remodeling in the ovine model. In doing so, 28 skeletally mature Columbia-Rambouillet cross ewes underwent an ovariectomy. The animals were divided into groups of 7 based on each season: autumn, winter, spring, and summer. During its specified season each group of 7 underwent ovariectomy and then was sacrificed 12 months post-surgery. The radii and ulnae were harvested and then divided into 6 anatomical locations: craniolateral, cranial, craniomedial, craniolateral, caudal, and caudomedial. This allowed for analysis through the fabrication of microradiographs. Histomorphometric analysis involved measurements to quantify the bone volume to tissue volume ratio, the percent of tissue and material remodeling, the mean secondary osteonal radius, and number of tissue and material cement line interfaces. Densitometry analysis was then performed to determine the density of each sector relative to an aluminum step wedge, serving as the key. Using a 2-way repeated measures ANOVA statistical analysis was performed to evaluate for seasonal and anatomical differences as well as a possible interaction between season and anatomical region. The OVX data showed significant seasonal and anatomical differences as well as seasonality within anatomical section in the remodeling parameters. When this data was combined with earlier data from a control, sham-cohort from the same experiment a 3-way ANOVA was also performed to evaluate the effects of season, anatomical sector, and treatment on the remodeling parameters. Again, there was significant seasonal, anatomical, and treatment differences, as well as interactions of all three. The results of this study showed that varying levels of remodeling occurs in the adult OVX ovine model and differences between the control and OVX model can be attributed to seasonal and anatomical variations. Thus, it will be an important consideration when developing new test protocols for research incorporating the sheep model for studying osteoporosis.

Falls among the elderly are a major source of injury, often leading to serious fractures, hospitalization, and death. Osteoporosis (OP) is a global problem intimately related with these fractures, characterized by reduced bone mass, increased bone fragility. There exists a high failure rate in the translation of treatments to osteoporotic populations. Mesenchymal stromal cell (MSC) transplantation as a therapeutic strategy for OP has not yet been examined in clinical trials. This may be attributed to the mixed findings of pre-clinical studies aimed at determining the efficacy of MSC therapy towards bone regeneration in OP. The most common animal model of OP is ovariectomy (OVX) that simulates post-menopausal estrogen loss. A plethora of bone regeneration studies have used OVX models with 12-16 weeks post-OVX periods and have generally reported positive results from a variety of treatment modalities, including MSC therapy. However, the use of the minimum post-OVX period may not be appropriate to reflect the global changes in regenerative potential of OP patients. In our research group's previous study, MSC were isolated from a minimum 60 week post-OVX rat model, representing a severe case of OP. The MSC isolated from these animals are a unique cell population that we expect may better represent the outcomes of autologous cell therapies for the older patient population in the clinic. In the present study, adipose and bone marrow derived MSC from OVX and age-matched animals were evaluated for their osteogenic and adipogenic differentiation potentials in culture through passage 10. Results from this study suggest that bone marrow derived-MSC maintain their phenotype and functionality more effectively than adipose derived-MSC in OP. Further investigations used regenerative medicine approaches for cell expansion on keratin protein coated microcarriers in static culture. Hair-derived keratin biomaterials have demonstrated their utility as carriers of biologics and drugs for tissue engineering. An optimal microcarrier was selected that demonstrated superior retention of the protein coating through electrostatic interactions and high cell viability. Finally, the integration of cell-microcarriers into a perfusion bioreactor system was explored. Preliminary results demonstrated the feasibility of MSC growth and differentiation on microcarrier based packed beds. Moreover, AD-MSC from OP rats were unresponsive to both inductive media and shear stress related osteogenic cues. These results highlight the complexity and challenges associated with the MSC regenerative strategy. / Doctor of Philosophy / Osteoporosis is a skeletal disease that results in reduced bone mass, increased bone fragility and fracture risk. Osteoporotic patients who experience falls suffer serious fractures, hospitalization, and poor bone healing. Several different therapies have been developed for the treatment of osteoporosis, though many are unable to translate from the bench to the clinical population. A popular treatment being investigated is the application of mesenchymal stromal cells (MSC) for fracture repair and the reversal of osteoporotic bone losses. However, cells isolated from aged and osteoporotic patients have been shown to have deficient bone forming properties. Nevertheless, animal models of osteoporosis applying this treatment report amelioration of bone loss. This work seeks to examine a more clinically relevant rat model of osteoporosis. Typical osteoporosis models use an ovariectomy procedure to simulate post-menopausal bone loss on relatively young animals and conduct short-term studies. These studies may not accurately reflect the global regenerative changes in osteoporosis patients or the impaired MSC properties. Adipose and bone marrow derived MSC from a long term ovariectomy model were investigated for their regenerative potentials. MSC growth and bone forming potential was evaluated on keratin protein coated microcarriers in both static and perfusion cultures. Results from this study suggest that bone marrow derived MSC maintain their phenotype and functionality more effectively than adipose derived MSC in osteoporosis. Further preliminary results demonstrated the feasibility of MSC growth and differentiation on microcarrier based packed beds. These results highlight the complexity and challenges associated with the MSC regenerative strategy.

published_or_final_version / abstract / Physiology / Doctoral / Doctor of Philosophy

Avaliamos as propriedades mecânicas, obtidas através de ensaios de flexo-compressão de fêmures e flexão em 3 pontos de tíbias de ratas adultas ovariectomizadas e submetidas à atividade física. Para realização do experimento foram utilizadas 30 ratas divididas aleatoriamente em 3 grupos: Grupo 1 – controle. Grupo 2: constituído por animais ovariectomizados e não submetidos à atividade física. Grupo 3: os animais deste grupo foram treinados em uma gaiola giratória por cinco dias consecutivos, em seguida foram submetidos a ovariectomia, permanecendo em repouso por 24 horas. Foram colocados para prática de atividade física por 30 minutos, 5 dias por semana durante 9 semanas com velocidade de aproximadamente 0,31 m/s. Os fêmures tiveram a porção distal incluída em resina acrílica para que fosse efetuado o ensaio de flexo-compressão. As tíbias foram submetidas ao ensaio de flexão em 3 pontos. Através dos resultados obtidos foram elaborados gráficos de carga versus deformação que evidenciaram que os fêmures das ratas ovariectomizadas apresentaram redução estatisticamente significativa nas propriedades mecânicas de carga no limite máximo e de deformação no limite máximo. Os fêmures do grupo ovariectomizado e submetido à prática de atividade física apresentaram valores de carga no limite máximo e de deformação no limite máximo superiores aos do grupo apenas ovariectomizado, no entanto, sem significância estatística. As tíbias não apresentaram alterações significativas em nenhuma das propriedades mecânicas estudadas. A atividade física aplicada por 30 minutos, 5 dias por semana durante 9 semanas a 0,31 m/s não foi suficiente para corrigir as alterações biomecânicas do tecido ósseo provocadas pela ovariectomia / We evaluated the mechanical properties, obtained by essays of flexion-compression of femurs and flexion in 3 points of tibiae of adult female ovariectomized rats and exposed to physical activity. To perform this experiment 30 rats divided randomly in three groups were used: Group 1 – control. Group 2: formed by ovariectomized animals, not submitted to physical activity. Group 3: the animals in this group were trained in a treadmill for 5 consecutive days and then submitted to the ovariectomy, remaining in rest for 24 hours. They were submitted to physical activity for 30 minutes with a velocity of 0,31 m/s, five days a week during 9 weeks. The femurs had their distal portion included in acrilic resinous so that the essay of flexion-compression could be done. And the tibiae were submitted to the flexion essay in 3 points. Based on the results, graphics on the cargo versus deformation, which showed that the femurs of the ovariectomized rats presented a statisticaly significant reduction in its mechanical properties of maximun cargo and maximun deformation. The femurs of the ovariectomized group and submitted to the physical activity presented higher values of maximun cargo and maximun deformation, than the group that was just ovariectomized, however, with no statistical importance. The tibiae did not present significant alterations in any of the mechanical properties studied. The physical activity applied for 30 minutes, 5 days a week during 9 weeks with a velocity of 0,31 m/s was not enought to correct the biomechanical alterations of the bone tissue caused by the ovariectomy

O objetivo do presente estudo foi avaliar ossos maxilares e lesões periapicais induzidas em ratas ovariectomizadas submetidas ou não ao tratamento com bisfosfonato (Alendronato - ALD) ou com inibidor da catepsina K (Odanacatib - ODN). Foram utilizadas 45 ratas, divididas em 6 grupos: I sham (cirurgia de ovariectomia fictícia); II sham e lesão periapical (LP); III - ovariectomia (OVX) sem LP; IV OVX e LP; V OVX, LP e ALD; e Grupo VI - OVX, LP e ODN. Um dia após a realização da OVX ou da cirurgia fictícia, os animais dos grupos V e VI começaram a receber ALD ou ODN, via gavagem. Decorridas 9 semanas da realização da OVX, os primeiros molares dos grupos II, IV, V e VI foram submetidos à indução de LP por 3 semanas. Decorrido este período, foi realizada colheita microbiológica dos canais radiculares para a quantificação de micro-organismos e os animais foram submetidos à eutanásia. Fêmures foram analisados por meio de densitômetro, para registro da densidade mineral óssea (BMD). As maxilas foram analisadas por meio de microtomografia computadorizada (micro-CT) para avaliação da microarquitetura e BMD do osso interradicular e as mandíbulas para avaliação do volume das LP. Os primeiros molares inferiores foram submetidos ao processamento histotécnico, sendo os cortes corados com hematoxilina e eosina (HE) e analisados em microscopia convencional. Paralelamente, foi realizada a análise morfométrica da área das lesões periapicais, em microscopia de fluorescência e histoenzimologia para a atividade da TRAP. Os primeiros molares superiores foram submetidos à detecção da expressão gênica de citocinas, marcadores da osteoclastogênese e de metaloproteinases da matriz. Os resultados obtidos foram submetidos à análise estatística apropriada, com nível de significância de 5%. A OVX afetou a BMD do fêmur e da maxila e a microarquitetura apenas do fêmur. O ALD recuperou a BMD dos ossos avaliados. A OVX não foi capaz de influenciar nos níveis de contaminação microbiana do canal radicular. As LP dos animais do grupo IV apresentaram expressão aumentada de RANK, RANKL, IL-1β, IL-6, TNF-α, MMP-8 e 13, enquanto o tratamento com ALD (grupo V) foi capaz de reduzir a expressão de IL-6 e MMP-8, ao mesmo nível que nas LP do grupo II. Além disso, as LP do grupo IV foram maiores (área e volume), em comparação às dos grupos II e V. O ODN, na dose e frequência de administração aplicada, não foi capaz de promover alterações significantes. A OVX e os tratamentos antirreabsortivos não influenciaram no número de osteoclastos ao redor da LP. Assim, concluiu-se que a condição hipoestrogênica induzida pela OVX foi capaz de diminuir a BMD do fêmur e da maxila e alterou a microarquitetura do fêmur. Apenas o ALD foi capaz de recuperar o fenótipo da BMD, ou seja, retorno aos níveis observados nos animais saudáveis. Ainda, a OVX agravou o processo de reabsorção, a inflamação e a expressão de MMPs, provocando lesões periapicais maiores. O ALD e o ODN proporcionaram uma melhora da resposta periapical. Entretanto, apenas o tratamento com ALD recuperou o fenótipo, fazendo com que as lesões periapicais fossem similares às lesões dos animais saudáveis. / The aim of this study was to evaluate maxillary bones and apical periodontitis induced in ovariectomized rats treated or not with bisphosphonate (Alendronate - ALD) or cathepsin K inhibitor (Odanacatib - ODN). Forty-five female rats were divided into 6 groups: I sham surgery; II - sham and apical periodontitis (AP); III - ovariectomy (OVX) without AP; IV - OVX and AP; V - OVX, AP and ALD; and Group VI - OVX, AP and ODN. One day after OVX or sham surgery, the animals in groups V and VI started receiving ALD or ODN, by gavage. After 9 weeks, the first molars of the rats in groups II, IV, V and VI were subjected to induction of AP for 3 weeks. Microbiological root canal sampling was collected for quantification of microorganisms and the animals were euthanized. Bone mineral density (BMD) of the femurs was analyzed by bone densitometry. The maxillas were analyzed by microcomputed tomography (micro-CT) to determine the microarchitecture and BMD of the interradicular bone while the mandibles were analyzed to determined AP volume. The mandibular first molars were subjected to histotechnical processing and hematoxylin and eosin-stained histological sections were examined with conventional microscopy. In addition, a morphometric analysis of AP area was performed using fluorescence microscopy and tartrate-resistant acid phosphatase (TRAP) histoenzymology. The maxillary first molars were used to evaluate the gene expression of cytokines, osteoclastogenesis markers and matrix metalloproteinases (MMP) using RT-PCR. The results were subjected to appropriate statistical analysis with 5% significance level. OVX affected femoral and maxillary BMD and femoral microarchitecture. ALD recovered the BMD of both types of bones. OVX was not able to influence the microbial levels of the root canal. In group IV, AP showed increased expression of RANK, RANKL, IL-1β, IL-6, TNF-α, MMP-8 and MMP-13, while ALD treatment (group V) reduced IL-6 and MMP-8 expression to the same level as the AP in group II. In group IV, AP area and volume were larger than in groups II and V. ODN, in the dosage and frequency of administration applied, was not able to promote significant changes. OVX and antiresorptive treatments did not influence the number of osteoclasts around the AP region. In conclusion, the hypoestrogenic condition induced by OVX was able to decrease the BMD of femur and maxilla and only the microarchitecture of the femur. ALD was able to recover the BMD phenotype, i.e., return to the levels observed in healthy animals. Furthermore, OVX exacerbated resorption, inflammation and MMP expression, inducing larger lesions. Treatment with ALD and ODN resulted in an improvement of the periapical response. However, only ALD recovered the phenotype, with AP similar to that of healthy animals.

O osso é um tecido dinâmico que remodela em resposta a um estímulo mecânico aplicado. O ultra-som pulsado de baixa intensidade consiste da propagação de ondas de energia mecânica e o propósito desta investigação foi analisar seus efeitos em um modelo ósseo de ratas ovarectomizadas por meio do ensaio de flexo-compressão. O estudo foi composto por 28 ratas Wistar, com peso médio de 251,4 gramas. Os animais foram divididos em 3 grupos: 10 animais ovarectomizados, tratados com ultra-som (grupo tratado), 9 animais ovarectomizados para controle (grupo ovarectomizado) e 9 animais intactos que não sofreram nenhum tipo de intervenção (grupo intacto). No grupo tratado as aplicações do ultra-som foram iniciadas no primeiro dia após a cirurgia de ovarectomia, extendendo-se por 9 semanas, 6 dias por semana, durante 20 minutos diários. Por meio do ensaio de flexo-compressão, realizado na extremidade proximal dos fêmures, foi avaliado o limite máximo. A deformação do limite máximo não foi alterada nos diferentes grupos. No entanto, a média da carga do limite máximo do grupo ovarectomizado foi significativamente menor quando comparada com os grupos intacto e tratado, e entre os grupos intacto e tratado as médias não foram estatisticamente diferentes, sugerindo que apesar do grupo tratado também ter sido submetido à ovarectomia, a média da carga do limite máximo foi semelhante à do grupo intacto pela influência do ultra-som. Estes resultados fornecem indícios de que a perda de massa óssea provocou diminuição da carga do limite máximo e que a estimulação com ultra-som pulsado de baixa intensidade em fêmures de ratas ovarectomizadas contribuiu na preservação deste parâmetro mecânico / Bone is a dynamic tissue, which remodels to applied mechanical stimuli. The low-intensity pulsed ultrasound consists on the propagation of waves of mechanical energy and the motivation of this study was to analyze its effects on a ovariectomized female rat bone model through flexion-compression test. The study was carried out with 28 female Wistar rats with 251,4 grams average weight. The animals were divided in 3 groups: 10 ovariectomized rats exposed to ultrasound (treated animals), 9 control ovariectomized animals (ovariectomized group) and 9 intact animals that did not suffer any kind of intervention (intact group). In the treated group, the ultrasound exposition was initiated on the first day after the surgery, and it was extended for 9 weeks, 6 days per week, during 20 minutes per day. Through the flexion-compression test, carried out on the femur’s proximal extremity, the maximum limit was evaluated. The maximum limit deformation wasn’t altered in these different groups. Though, the maximum limit load average in the ovariectomized group was significantly lower when compared to the intact and treated groups, and between the intact and treated groups, the average wasn’t statistically different, suggesting that despite of the treated group was submitted to ovariectomy, the average value of the load maximum limit was similar to the intact group by the ultrasound influence. These results were indications that the loss of bone mass caused the load maximum limit decreasing and that the low-intensity pulsed ultrasound stimulation on femurs of ovariectomized female rats contributed to the preservation of this mechanical parameter

Os efeitos vasculares da associação de estrogênios e testosterona, utilizada para tratamento do distúrbio de desejo sexual hipoativo na pós-menopausa ainda não estão elucidados. O objetivo do trabalho foi avaliar as respostas vasculares ao tratamento de ratas espontaneamente hipertensas ovariectomizadas (SHR-OVX) com o conjugado estrogênio equino (CEE) associado ou não a cipionato de testosterona (CEE+T). O tratamento de SHR-OVX com CEE promove melhora da função endotelial na aorta por mecanismos que envolvem a redução da geração de espécies reativas de oxigênio (EROs) e aumento da expressão proteica de enzimas antioxidantes. O tratamento com CEE+T inibe os efeitos vasculoprotetores do CEE sobre o endotélio, aumentando a geração de EROs e diminuindo a expressão da enzima óxido nítrico sintase. A maior geração de EROs na aorta do grupo CEE+T parece depender da ativação de receptores AT1 de angiotensina II, da maior ação de fator inflamatório o 20-HETE e da ativação da enzima NADPH oxidase. / The vascular effects of estrogens and testosterone association, used for hypoactive sexual desire disorder treatment in postmenopausal women, have not been elucidated. The aim of this study was to evaluate the vascular effects of female ovariectomized (OVX) SHR treatment with conjugated equine estrogen (CEE) associated or not with testosterone cypionate (CEE+T). Our data shows that treatment of OVX-SHR with CEE improved endothelial function reducing reactive oxygen species (ROS) generation and increasing some antioxidant cellular mechanisms. Treatment with CEE+T blunted the vascular effects of CEE, increasing ROS generation and reducing eNOS expression. The increased ROS in CEE+T rats aorta seems to involve in angiotensin II-AT1 activation, 20-HETE action and NADPH oxidase activation.

Algumas serpentes necessitam obrigatoriamente estocar espermatozoides nos ovidutos para que os oócitos sejam fecundados, isso porque nessas espécies o período de cópula é distinto do período de ovulação. Em geral essa estocagem ocorre em receptáculos de estocagem encontrados na região infundibular. Em Crotalíneos a estocagem tem sido descrita como ocorrendo na região caudal dos ovidutos (junção útero-vaginal) em uma estrutura chamada de Uterine Muscular Twisting (UMT). Essa estrutura tem sido descrita como um twisting que se forma após a cópula e permanece presente até o momento da ovulação. Aqui demonstramos que a UMT não é formado por uma torção (twist) do oviduto e sim por uma helicoide formada pelas camadas internas da junção útero-vaginal. A UMT está presente em fêmeas ao longo de todo o ano, e não somente no período pós-cópula. Nós observamos que a UMT tem diferentes graus de formação, podendo ser forte, fraca ou ausente. A UMT forte é encontrada no periodo reprodutivo da fêmea (outono e inverno austrais) e está presente independentemente de haver espermatozoides nessa região. A UMT fraca é encontrada em todas as fêmeas maduras fora do período reprodutivo. Já a ausencia de UMT é encontrada nas fêmeas prenhes e nas imaturas. Nossos resultados mostram que a UMT é formada mesmo em fêmeas ovariectomizadas com níveis basais de estradiol e que a progesterona é responsável pelo relaxamento da musculatura lisa do oviduto tornando a UMT ausente nas fêmeas / Some snakes need must store sperm in the oviduct so that the oocytes are fertilized, that because these species the mating period is distinct from ovulation period. Usually this occurs in receptacles found in the infundibular region. In pitvipers the storage has been described as occurring in the caudal region of oviduct (uterus-vaginal junction) in a structure named Uterine Muscular Twisting (UMT). This structure has been described as a twisting formed after mating and remains present until the time of ovulation. Here we demonstrate that the UMT is not formed by a twist (rotation around its own axis) of the oviduct but by a helicoid formed by the inner layers of the uterus-vaginal junction. The UMT is present in females throughout the whole year, not only in the post-copulation period. We note that the UMT has different degrees of shaping, can be strong, weak or absent. Strong UMT is found in the female reproductive period (austral autumn and winter) and is present regardless of whether sperm cells in this region. Weak UMT is found in all mature females outside the breeding season. Already the absence of UMT is found in pregnant females and the immature ones. Our results show that the UMT is formed even in ovariectomized with basal levels of estradiol and progesterone is responsible for relaxation of smooth muscle of the oviduct making UMT absent in females

Introdução: A doxiciclina, membro da família das tetraciclinas, é uma droga utilizada como antibiótico (posologia de 100 mg/dia) e como inibidora de metaloproteinases de matriz - MMPs - (posologia de 20 mg duas vezes ao dia), uso que tem efeito de droga anti-inflamatória. A doxiciclina é quelante de cálcio e portanto interfere na remodelação óssea. Objetiva-se neste trabalho avaliar ação do medicamento doxiciclina no controle da osteopenia. Materiais e métodos: 63 ratas Wistars obtidas no biotério central da Universidade de São Paulo campus de Ribeirão Preto foram divididas em 9 grupos com n=7 cada, sendo estes: grupo Controle com doxiciclina 10mg/kg/dia (C10), Controle com doxiciclina 30 mg/kg/dia (C30) e Controle (C), Grupo Ovariectomizado com doxiciclina 10mg/kg/dia (OVX10), Ovariectomizado com doxiciclina 30mg/kg/dia (OVX30) e Ovariectomizado com água (OVX), Grupo Sedentarismo 10mg/kg/dia (Se10), Sedentarismo 30mg/kg/dia (Se30) e Sedentário com água (Se). Todos os grupos tiveram seus modelos de indução a osteopenia por 90 dias. Em seguida, os grupos que receberam o medicamento, foram submetidos as doses diárias (10mg/kg/dia e 30mg/kg/dia) por 60 dias. As amostras dos fêmures esquerdos foram destinadas para densitometria óssea enquanto as amostras de fêmures direitos foram submetidos a análises de microscopia de luz. As amostras de tíbia direita foram destinadas à quantificação química de cálcio, magnésio, zinco e fósforo e, amostras de soro total foram submetidos a análises de quantificação de cálcio e colesterol total. O peso das ratas foi aferido em balança de precisão no próprio biotério. O fêmur esquerdo foi posteriormente seco em estufa a 37 graus Celsius e pesado em balança de precisão e o comprimento destes ossos fêmures foram aferidos com auxílio de um paquímetro digital para medição dos ossos em seu longo eixo. Foi empregada análise estatística modelo linear geral, multivariado e as análises de TRAP foram submetidas a teste de normalidade e em seguida à teste não paramétricos com Kurskal Wallis com análise de variância, havendo diferenças o post-test de Dunn foi realizado para especificar as diferenças ambas com significância de p<=0,05. Resultados: Foram encontradas diferenças estatisticamente significantes entre Se vs. Se10 e Se30 para BMC, quantificação de Magnésio e quantificação do trabeculado ósseo por Tricromo de Masson na porção distal, OVX vs. OVX10 para densitometria óssea e Cálcio em soro, OVX vs. OVX10 e OVX30 para quantificação de trabeculado ósseo por Tricromo de Masson na porção proximal e distal e Se vs. Se30 e OVX vs. OVX30 para imunomarcação por TRAP, todos os resultados com p<=0,05. Conclusão: Neste modelo experimental a doxiciclina teve um papel chave no transporte sanguíneo do quelato de cálcio (dados comprovados pela maior presença de cálcio no soro do grupo OVX30) e contribuiu positivamente em ossos de ratas acometidas pela osteopenia induzida por ovariectomia bilateral e sedentarismo, dados comprovados por densitometria, quantificação do trabeculado ósseo de fêmur porção distal, análise qualitativa por imunomarcação por TRAP e quantificação de Mg no osso. / Introduction: Doxycycline, a member of the tetracycline family, is a drug used as an antibiotic (100 mg / day dosage) and as an inhibitor of matrix metalloproteinases - MMPs (20 mg twice daily), a use that has anti-inflammatory effect. Doxycycline is a calcium chelator and therefore interferes with bone remodeling. The main objective of this study was to evaluate the action of the drug doxycycline in the control of osteopenia. Materials and methods: Sixty-three Wistars rats obtained from the USP, campus Ribeirão Preto, were divided into 9 groups with n = 7 each, being: Control group with Doxycycline 10 mg/kg/day (C10), Control with Doxycycline 30 mg/kg/day (OVX10), Ovariectomized with Doxycycline 30mg/kg/day (OVX30) and Ovariectomized with water (OVX), Sedentarism Group 10mg/kg/day (C30) and Control (C30), Ovariectomized Group with Doxycycline 10mg/kg/day (Se10), sedentarism 30mg/kg/day (Se30) and Sedentarism with water (Se). All groups had their induction models to osteopenia for 90 days. Subsequently, the groups receiving the medication were submitted to daily doses (10mg/kg/day and 30mg/kg/day) for 60 days. The left femur samples were assigned to Bone Densitometry, right femur samples were subjected to light microscopy, right tibia samples for chemical quantification of calcium, magnesium, zinc and phosphorus, and total serum samples were submitted to quantification of calcium and total cholesterol. The weight of the rats was measured on a precision scale at the animal house. The left femur was dried at 37 degrees Celsius on dried oven and then weighed on a precision scale, and the length of these femur bones were measured using a digital caliper to measure the bones along its long axis. Statistical analysis was used for linear general model, multivariate analysis and the TRAP analyzes were submitted to normality test and then to non-parametric test with Kurskal Wallis with analysis of variance, having differences a Dunn post-test was performed to specify the differences both with significance of p<=0.05. Results: Statistically significant differences were found between Se vs. Se10 and Se30 for BMC, quantification of Magnesium and quantification of bone trabeculation by Masson trichrome in the distal portion, OVX vs. OVX10 for bone densitometry and Calcium in serum, OVX vs. OVX10 and OVX30 for quantification of bone trabeculation by Masson trichrome in the proximal and distal portion and Se vs. Se30 and OVX vs. OVX30 for TRAP immunostaining, all results with p<=0.05. Conclusion: At this experimental model, doxycycline played a key role in the blood transport of calcium chelate (data evidenced by the higher presence of calcium in the serum of the OVX30 group) and contributed positively to bone from rats affected by osteopenia induced by bilateral ovariectomy and sedentary lifestyle, supporting data of bone densitometry, quantification of bone trabeculation of the distal femur, qualitative analysis by TRAP immunostaining and quantification of Mg in the bone.