Cartilage regeneration is one of the most widely studied areas in tissue-engineering. Despite significant progress, most efforts to date have only focused on generating homogenous tissues whose bulk properties are similar to articular cartilage. However, anatomically and functionally, articular cartilage consists of four spatially distinct regions: the superficial, transitional, deep, and calcified zones. Each zone is characterized by unique extra-cellular matrix (ECM) compositions, mechanical properties, and cellular organization. The ECM is primarily composed of type II collagen and glycosaminoglycans (GAGs), whose relative concentrations vary between zones and therefore lead to distinctive mechanical properties. One of the major unsolved challenges in engineering cartilage has been the inability to regenerate tissue that mimics the zonal architecture of articular cartilage. Recent studies have attempted to imitate this spatial organization using zone-specific chondrocytes isolated from donor animal cartilage. Directed differentiation of a single stem population into zonally organized native-like articular cartilage has not yet been reported. This dissertation reports that hydrogels, incorporating both synthetic and natural polymers as well as cell-induced degradability, are suitable for generating zone-specific chondrogenic phenotypes from a single MSC population. Specifically, cues provided from the unique combinations of chondroitin sulfate (CS), hyaluronic acid (HA), and MMP-sensitive peptide (MMP-pep) within a PEG-based hydrogel, direct the chondrogenic differentiation of MSCs. The findings of this dissertation demonstrate the capability of creating native-like and mechanically relevant articular cartilage consisting of zone specific layers. This ability provides a new direction in cartilage tissue engineering and could be invaluable for cartilage repair if incorporated with current minimally invasive surgical techniques. / text

The development of bioengineered cartilage for replacement of damaged articular cartilage has gained momentum in recent years. One such approach has been developed in the Kandel lab, whereby cartilage is formed by seeding primary articular chondrocytes on the top surface of a porous biodegradable calcium polyphosphate (CPP) bone substitute, permitting anchorage of the tissue within the pores of the substrate; however, the interfacial shear properties of the tissue-substrate interface of these biphasic constructs are 1 to 2 orders of magnitude lower than the native cartilage-subchondral bone interface. To overcome this limitation, a strategy was devised to generate a zone of calcified cartilage (ZCC), thereby mimicking the native architecture of the osteochondral junction; however, the ZCC was located slightly above the cartilage-CPP interface. Thus, it was hypothesized that polyphosphate released from the CPP substrate and accumulating in the tissue inhibits the formation of the ZCC at the tissue-substrate interface. Based on this information, a strategy was devised to generate biphasic constructs incorporating a properly located ZCC. This approach involved the application of a thin calcium phosphate film to the surfaces of porous CPP via a sol-gel procedure, thereby limiting the accumulation of polyphosphate in the cartilaginous tissue. This modification to the substrate surface did not negatively impact the quality of the in vitro-formed cartilage tissue or the ZCC. Interfacial shear testing of biphasic constructs demonstrated significantly improved interfacial shear properties in the presence of a properly located ZCC. These studies also led to the observation that chondrocytes produce endogenous polyphosphate and that its levels in deep zone cartilage appear inversely related to mineral deposition within the tissue. Using an in vitro model of cartilage calcification, it was demonstrated that polyphosphate levels are modulated in part by the inhibitory effects of fibroblast growth factor 18 on exopolyphosphatase activity in the tissue. Polyphosphate also appears to act in a feedback loop to control exopolyphosphatase activity. Interestingly, polyphosphate also exhibits positive effects on cartilage matrix accumulation. The potential implication of polyphosphate in the maintenance of articular cartilage homeostasis is intriguing and must be investigated further.

The development of bioengineered cartilage for replacement of damaged articular cartilage has gained momentum in recent years. One such approach has been developed in the Kandel lab, whereby cartilage is formed by seeding primary articular chondrocytes on the top surface of a porous biodegradable calcium polyphosphate (CPP) bone substitute, permitting anchorage of the tissue within the pores of the substrate; however, the interfacial shear properties of the tissue-substrate interface of these biphasic constructs are 1 to 2 orders of magnitude lower than the native cartilage-subchondral bone interface. To overcome this limitation, a strategy was devised to generate a zone of calcified cartilage (ZCC), thereby mimicking the native architecture of the osteochondral junction; however, the ZCC was located slightly above the cartilage-CPP interface. Thus, it was hypothesized that polyphosphate released from the CPP substrate and accumulating in the tissue inhibits the formation of the ZCC at the tissue-substrate interface. Based on this information, a strategy was devised to generate biphasic constructs incorporating a properly located ZCC. This approach involved the application of a thin calcium phosphate film to the surfaces of porous CPP via a sol-gel procedure, thereby limiting the accumulation of polyphosphate in the cartilaginous tissue. This modification to the substrate surface did not negatively impact the quality of the in vitro-formed cartilage tissue or the ZCC. Interfacial shear testing of biphasic constructs demonstrated significantly improved interfacial shear properties in the presence of a properly located ZCC. These studies also led to the observation that chondrocytes produce endogenous polyphosphate and that its levels in deep zone cartilage appear inversely related to mineral deposition within the tissue. Using an in vitro model of cartilage calcification, it was demonstrated that polyphosphate levels are modulated in part by the inhibitory effects of fibroblast growth factor 18 on exopolyphosphatase activity in the tissue. Polyphosphate also appears to act in a feedback loop to control exopolyphosphatase activity. Interestingly, polyphosphate also exhibits positive effects on cartilage matrix accumulation. The potential implication of polyphosphate in the maintenance of articular cartilage homeostasis is intriguing and must be investigated further.

Articular cartilage on weight-bearing joints experiences three main forces: fluid-induced shear across the surface, perfusion through the cartilage from the surrounding fluid, and compression during motion of the joint. A new bioreactor that employs two of these forces was developed in this lab to study their effect on tissue-engineered cartilage development. The focus of this research and overall hypothesis is that bioreactors that employ both perfusion and shear will improve chondrogenesis and preservation to produce functionally relevant cartilage by modulating shear stress and introducing exogenous preservation factors. Applying both a low shear stress across the surface of cell-seeded scaffolds and perfusion through them in a perfusion concentric cylinder (PCC) bioreactor may stimulate chondrocytes to undergo chondrogenesis. Experimental data showed that the PCC bioreactor stimulated cartilage growth over the course of four weeks, supported by the appearance of glycosaminoglycan (GAG) and collagen type II, which are markers for articular cartilage. Computational fluid dynamics modeling showed that shear stress across the face of the construct was heterogeneous, and that only the center experienced a relatively uniform shear stress of 0.4 dynes/cm^2 when the outer cup of the bioreactor rotated at 38 rpm. When compared to a concentric cylinder (CC) bioreactor that employed only shear stress, the PCC bioreactor caused a significant increase in cellular proliferation, which resulted in a 12-fold increase in cell number per construct compared to 7-fold increase within the CC bioreactor. However, the PCC bioreactor had a less pronounced effect on glycosaminoglycan and collagen content with 1.3 mg of GAG and 1.8 mg of collagen per construct within the CC bioreactor and 0.7 mg of GAG and 0.8 mg of collagen per construct within the PCC bioreactor after 28 days in culture (p < 0.05). Our results led to an important observation that the PCC bioreactor affected cellular proliferation significantly but not extracellular matrix synthesis. The next objective of this study focused on the PCC bioreactor to evaluate the direct role of perfusion and shear on chondrogenesis in vitro and in vivo.

Osteoarthritis is a degenerative joint disease characterized by progressive erosion of the articular cartilage. Epidemiological studies have established a relationship between osteoarthritis and menopause suggesting that estrogen may be important in the development of cartilage regeneration therapies. The overall goal of this research project was to advance the field of cartilage tissue regeneration by investigating the role of 17 ß -estradiol (E2), an active estrogen metabolite, on the chondrocyte phenotype. The central hypothesis was that E2 plays an important and sex-specific role in regulating chondrogenesis. Specific Aim-1 focused on establishing and characterizing a primary human articular chondrocyte (HAC) cell source, and then examining the response of the cells in culture to E2. It was demonstrated that the response of HACs to E2 treatment was sex-specific despite both male and females cells expressing estrogen receptors. Female HACs showed changes in proliferation, matrix production, and differentiation while male cells did not. In addition, the female response was regulated through a rapid membrane signaling pathway mediated by protein kinase C. Specific Aim-2 involved establishing an ovariectomized animal model to investigate the effects of E2 on orthopaedic tissue implants. Human demineralized bone matrix (DBM) was implanted intramuscularly into female nude mice and rats. Ovariectomy was shown to reduce the ability of DBM to induce the formation of cartilage and bone tissue. Moreover, the inductive properties of DBM were reestablished with subcutaneous E2 supplementation. Specific Aim-3 entailed developing and characterizing a microencapsulation method for in vitro culture and in vivo delivery of chondrocytes to study the effects of E2 on chondrogenesis. Rat growth plate chondrocytes and HACs were microencapsulated in alginate using an extrusion method in conjunction with high electrostatic potential. Chondrocytes maintained their phenotype in alginate suspension but were unable to form cartilage tissue when implanted into our animal model. Further optimization of the system is required before the role of E2 on chondrogenesis of tissue engineered constructs can be determined. In summary, our results suggest that the successful production of tissue engineered therapies will likely depend on understanding and manipulating the actions of sex hormones in both the in vitro and in vivo environment.

[Truncated abstract] Hyaline articular cartilage is a highly specialised tissue consisting of chondrocytes embedded in a matrix of proteoglycan and collagens. Hyaline articular cartilage withstands high levels of mechanical stress and continuously renews its extracellular matrix. Despite this durability, mature articular cartilage is vulnerable to injury and disease processes that cause irreparable tissue damage. Native hyaline articular cartilage has poor regenerative capacity following injury, largely due to the tissue's lack of blood and lymphatic supply, as well as the inability of native chondrocytes to migrate through the dense extracellular matrix into the defect site. Articular cartilage injuries that fail to penetrate the subchondral bone plate evoke only a short-lived metabolic and enzymatic response, which fails to provide sufficient new cells or matrix to repair even minimal damage. Clinically, it has previously been accepted that treatment of such defects does not result in the restoration of normal hyaline articular cartilage, which is able to withstand the mechanical demands that are placed on the joint during every day activities of daily living. ... Historically, rehabilitation following ACI has not kept pace with the advances in cell culture and surgical technique. Subsequently, there exists a significant gap in knowledge regarding `best practice' in post operative rehabilitation following ACI. The importance of structured rehabilitation in ACI should not be underestimated when evaluating the clinical success of this chondral treatment. Patients should not be left to their own devices following ACI surgery, as the risk of damage to their implant (via delamination) is high if immediate postoperative movement is not controlled. Furthermore, the biological longevity and clinical success of the graft is dependent on a controlled and graduated return to ambulation and physical activity, and the biomechanical stimulation of the implanted chondrocytes.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2008. / Härtill 4 uppsatser.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Generalized joint hypermobility (GJH) is an extreme variation of normal joint mobility and it is considered a benign and non- pathological phenomenon. Among its manifestations are the reduction of the proprioception and, consequently, of the motor coordination. It is believed that the temporomandibular joint (TMJ) is amongst the joints affected by GJH . This fact instigated this research, which propose to evaluate the influence of GJH on the TMJ, the stomatognathic functions of mastication and deglutition, and dental occlusion in women. Forty three women participated, voluntarily, in the study conducted at the Speech-Language-Hearing Service of UFSM. The HAG was assessed according to the criteria of Carter and Wilkinson, modified by Beighton and, based on the scores obtained in this scale, the volunteers were distributed into two groups: with GJH (GH, n=17) and without GJH (GSH, n=26). The signs of TMD were examined according the instrument Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD); mastication and deglutition were assessed through myofunctional orofacial exam (MBGR protocol Marchesan, Berretin-Felix, Genaro, Rehder, 2009); and the occlusion evaluation comprised: the Angle Class, presence of overbite, overjet, openbite or crossbite, pattern of desocclusion and occlusal interference. The analyzed results showed prevalence of clicks during jaw movements (52.9%) and mouth opening deviation (76.5%) in the GH. The mastication pattern appeared abnormal in 48,1% of volunteers of GH, and there was a significant association between the mastication pattern and the mouth opening pattern, only in the GSH (p=0.05). Regarding occlusion, no volunteer had an ideal occlusion and there was no significant difference between the groups in the Angle Class. Higher percentage of changes in the occlusion was observed in the GH (29.4 % of overbite, 47.1% of overjet and 17.6% of crossbite), with statistically difference of crossbite in the GH (p=0.05). These findings suggest that women with GJH have a reduction of the proprioception and, consequent impairment of the joint stability and the neuromuscular coordination. Moreover, the occlusal changes in women with GJH may be resulting from the connective tissue fragility present in this condition. / A hipermobilidade articular generalizada (HAG) representa uma variação extrema da mobilidade articular normal e é considerada um fenômeno benigno e não patológico. Entre as suas manifestações estão a redução da propriocepção, e consequentemente, da coordenação motora. Acredita-se que a articulação temporomandibular (ATM) esteja entre as articulações acometidas pela HAG. Este fato instigou esta pesquisa, que se propôs avaliar a influência da HAG sobre a ATM, as funções estomatognáticas de mastigação e deglutição e a oclusão dentária em mulheres. 43 mulheres participaram, voluntariamente, da pesquisa, realizada no Serviço de Atendimento Fonoaudiológico da UFSM. A HAG foi avaliada conforme os critérios de Carter e Wilkinson, modificados por Beighton e, a partir dos escores obtidos nessa escala, as voluntárias foram distribuídas em dois grupos: com HAG (GH n=17) e sem HAG (GSH n=26). Os sinais de DTM foram examinados conforme o instrumento Critérios de Diagnóstico para Pesquisa de Desordens Temporomandibulares (RDC/TMD); as funções de mastigação e deglutição foram avaliadas por meio do exame miofuncional orofacial (protocolo MBGR Marchesan, Berretin-Felix, Genaro, Rehder, 2009); e a avaliação da oclusão compreendeu a classificação de Angle, presença de sobremordida, sobressaliência, mordida aberta ou cruzada, padrão de desoclusão e interferências oclusais. Os resultados analisados demonstraram predomínio de ruídos articulares durante movimentos mandibulares (52,9%) e de desvio na abertura da boca (76,5%) nas voluntárias do GH. O padrão de mastigação apareceu alterado em 48,1% das voluntárias do GH, e foi verificada uma associação significativa entre o padrão de mastigação e de abertura da boca, apenas no GSH (p=0,05). Quanto à oclusão, nenhuma voluntária apresentou uma oclusão ideal e não se verificou diferença significativa na Classe de Angle entre os grupos. As alterações na oclusão obtiveram percentual maior no GH (29,4% de sobremordida, 47,1% de sobressaliência e 17,6% de mordida cruzada), com diferença significativa na mordida cruzada no GH (p=0,05). Estes achados sugerem que as mulheres com HAG apresentam uma redução da propriocepção e, consequente, comprometimento da estabilidade articular e coordenação neuromuscular. Além disso, as alterações oclusais em mulheres com HAG, podem ser decorrentes da fragilidade do tecido conjuntivo presente nessa condição.

Orientador: Paulo Renato Junqueira Zuim / Banca: Rafael dos Santos Silva / Banca: Karina HelgaTúrcio de Carvalho / Banca: Stefan Fiuza de Carvalho Dekon / Banca: Valdir de Sousa / Resumo: Disfunção temporomandibular (DTM) é definida como uma coleção de condições médicas, dentárias ou faciais associadas com anormalidades do sistema estomatognático, que desencadeiam desordens na articulação temporomandibular e tecidos adjacentes, incluindo os músculos faciais e cervicais. Hipermobilidade Articular Generalizada (HAG) é definida como uma alteração da normalidade em que articulações do corpo exercem uma mobilidade maior do que aquela anatomicamente considerada normal. O presente estudo apresenta importância relacionada à necessidade de maiores investigações sobre prevalência de DTM em jovens, uma vez que a maioria dos estudos voltados para DTM investiga indivíduos adultos, e também para averiguar a possível correlação entre entidades distintas, mas que parecem estar relacionadas: DTM x HAG. O objetivo do estudo é investigar a prevalência de DTM em indivíduos jovens e relacionar esta com hipermobilidade articular generalizada nesta mesma população. Todos os estudantes do curso de odontologia matriculados em uma universidade foram convidados a participar, como voluntários, do estudo proposto. Uma amostra de 100 indivíduos (72 mulheres e 28 homens) foi obtida. Todos os alunos foram submetidos a um exame denominado RDC / TMD que diagnostica presença de DTM. Dois grupos foram formados: Um primeiro grupo com indivíduos que apresentam DTM e outro grupo com indivíduos que não apresentam DTM. Depois disso os indivíduos do primeiro grupo foram subdivididos de acordo com o tipo de DTM apresentada. Em outra etapa, todos os 100 indivíduos foram submetidos ao exame de "índice de Beighton" com finalidade de diagnosticar presença de HAG. Depois destas investigações, foi realizada uma análise estatística entre os grupos com intuito inicial de verificar a prevalência de DTM nesta... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Temporomandibular disorder (TMD) is defined as a collection of medical conditions associated with dental or facial abnormalities of the stomatognathic system, triggering unrest in the temporomandibular joint and adjacent tissues, including facial and neck muscles. Generalized Joint Hypermobility (GJH) is defined as a change of normality in which the body's joints have a higher mobility than that considered anatomically normal. This study has importance related to the need for further investigation on the prevalence of TMD in young adults, since most studies focused on investigating TMD in adults, and also to investigate the possible correlation between distinct entities, but that appear to be related: Temporomandibular disorder and Generelized Joint Hypermobility. The aim of this study is to investigate the prevalence of TMD in young adults and to correlate this with generalized joint hypermobility in the same population. All students of a dental school enrolled in a university were invited to participate as volunteers to the proposed study. A sample of 100 individuals (72 women and 28 men) asymptomatic was obtained. All students underwent a test called RDC / TMD diagnosing TMD. Two groups were formed: One group of individuals who present TMD and another group with individuals who do not present TMD. After that, the individuals in the first group were subdivided according to the kind of TMD presented. In another step, all 100 subjects underwent an examination of "Beighton index" with the purpose of diagnosing the presence of GJH. After these investigations, we performed a statistical analysis between groups in order to verify the initial TMD prevalence in this population and subsequently correlated it with Generalized Joint Hypermobility (GJH). We obtained that: 100 patients examined, 24 individuals (24% - 23 women and 1 man) were... (Complete abstract click electronic access below) / Doutor

?rea de concentra??o: Ci?ncias Fisiol?gicas. / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2018-04-10T17:10:13Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) jeanne_brenda_martins.pdf: 1441533 bytes, checksum: d98402deb80597c80a5de929f7844c26 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-04-23T16:25:07Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) jeanne_brenda_martins.pdf: 1441533 bytes, checksum: d98402deb80597c80a5de929f7844c26 (MD5) / Made available in DSpace on 2018-04-23T16:25:07Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) jeanne_brenda_martins.pdf: 1441533 bytes, checksum: d98402deb80597c80a5de929f7844c26 (MD5) Previous issue date: 2017 / A osteoartrite ? uma doen?a articular degenerativa que causa dor, diminui??o da amplitude de movimento, perda de fun??o e incapacidade f?sica para executar as principais atividades de vida di?ria. O exerc?cio constitu?do por caminhada de intensidade moderada em esteira ? um dos tratamentos n?o farmacol?gicos da osteoartrite de joelho, mas seus efeitos especificamente em biomarcadores relacionados com degrada??o articular de joelho e poss?vel associa??o com funcionalidade permanecem inconclusivos. O objetivo do presente estudo foi avaliar os efeitos do treinamento com exerc?cio f?sico de intensidade moderada em esteira nos biomarcadores sist?micos de estresse oxidativo, par?metros inflamat?rios locais, no desempenho f?sico funcional, al?m de quantificar c?lulas da cartilagem em ratos com osteoartrite de joelho induzida. Materiais e m?todo: 27 ratos Wistar (433 + 18g, 12 semanas de idade) foram divididos em tr?s grupos (n = 9 por grupo): grupo sham (SHAM); grupo osteoartrite de joelho induzida (OA); grupo treinamento com exerc?cio f?sico e osteoartrite de joelho (OAT). A osteoartrite de joelho foi induzida por uma ?nica inje??o de monoiodoacetato de s?dio (MIA) na concentra??o de 1,2 mg. O treinamento f?sico foi progressivo (16 m/min-1 30-50 min/dia) e com frequ?ncia de 3 dias/semana durante 8 semanas. Vinte e quatro horas ap?s o ?ltimo dia de interven??o, todos os animais dos tr?s grupos realizaram testes funcionais incluindo n?mero de quedas durante o teste Rotarod, tempo e n?mero de falhas durante o deslocamento em plataforma de 100 cm. Em seguida, os ratos foram eutanasiados e materiais biol?gicos coletados para a avalia??o de biomarcadores articulares inflamat?rios e sist?micos para avalia??o do estado redox. A articula??o do joelho foi removida e utilizada para avalia??o histol?gica. Foram utilizados para analisar os dados o teste ANOVA oneway (p<0,05) seguido de post-hoc Tukey (dados param?tricos) ou Kruskal Wallis seguido de post-hoc de Dunn (n?o param?tricos). Modelos de regress?o linear m?ltipla stepwise foram aplicados a fim de verificar a associa??o entre biomarcadores e funcionalidade. Resultados: O grupo OAT apresentou maiores escores de desempenho funcional em todos os testes de fun??o articular (teste de Rota rod p = 0,002, tempo de falhas de deslocamento p = 0,005, n?mero de falhas de deslocamento p = 0,0002) comparado com os demais grupos. Observou-se redu??o nas concentra??es articulares dos biomarcadores de degrada??o articular (IL-1? p<0,0001, TNF-? p=0,0001) e aumento na concentra??o articular de BDNF no grupo OAT comparado ao grupo OA. Al?m disso, as concentra??es articulares das citocinas IL-6 (p<0,005) e IL-10 (p<0,0001) foram maiores no grupo OA comparado aos demais grupos. As concentra??es de ambos marcadores articulares (IL-1? e TNF-?) explicaram 58% da variabilidade do n?mero de quedas (p<0,001), ao passo que o TNF-? analisado isoladamente explicou 29% da variabilidade do tempo de deslocamento em percurso conhecido (p=0,002) e 21% da variabilidade do n?mero de quedas (p=0,01). Conclus?o: Todos os achados indicam a efic?cia do treinamento de intensidade moderada em esteira para reduzir a degrada??o articular de joelho com OA induzida, uma vez que modula biomarcadores locais inflamat?rios e sist?micos relacionados com estresse oxidativo. Al?m disso, esta modula??o em biomarcadores de degrada??o articular propiciou conserva??o celular que impactou positivamente na funcionalidade de ratos com osteoartrite de joelho induzida por monoiodoacetado de s?dio. / Disserta??o (Mestrado) ? Programa Multic?ntrico de P?s-gradua??o em Ci?ncias Fisiol?gicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / OBJECTIVE: The aim of this study was to evaluate the effect of moderate treadmill training on joint inflammatory profile and functional performance on induced knee OA in rats. METHODS: 27 male rats were divided into three groups of nine animals each: sham (SHAM); induced knee OA (OA); OA exercise training (OAT). The knee OA was induced by monosodium iodoacetate. The OAT group trained for 8 weeks. Functional tests including Rota rod test, displacement in footbridge of 100 cm were performed. The rigth joint lavage was used IL1?, TNF, IL10 analysis. Articular capsule of the same joint was used for BDNF and IL6 analysis. The left joint was used for histological analysis. Redox status was evaluated in plasma. RESULTS: Oxidative stress parameters and joint biomarkers inflammatory profile indicate the induction of knee OA. The OAT group presented a higher functional performance in all joint function tests, reduction of IL1 and TNF joint level, increase of BDNF joint level. The levels of both IL1 and TNF explained 58% of the variability of number of falls, while only TNF explained 29% of the variability of time of displacement and 21% of the variability of number of displacement failures. The histological data confirm the preservation rate of chondrocytes in the joint cartilage. CONCLUSION: Our results indicate the effectiveness of moderate treadmill training to reduce knee joint degradation associated to improving functionality of induced knee OA in rats. The greater cell conservation infers that this dose favored the attenuation of the degenerative process.