revisao cartilagem

8/12/2019 revisao cartilagem

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Cartilagem Condilar da Mandbula: uma RevisoThe M andibular Condylar Car t ilage: a Review

German O. Ramirez-Yaez 1

Ramirez-Yaez GO. Cartilagem condilar da mandbula: uma reviso. OrtopRev Int Ortop Func 2004; 1(1):85-94.

A cartilagem mandibular uma estrutura especializada presen-te na superfcie dos cndilos mandibulares. Tem duas funesprincipais: crescimento endocondral e funo articular. Essacartilagem composta de dois tipos: uma cartilagem fibrosa,cuja funo principal suportar as cargas, e uma cartilagemhialina, que participa principalmente na ossificao endocondrale no crescimento da mandbula. Este trabalho faz uma revisodo conhecimento atual sobre essa cartilagem especializada esua relao com a funo craniomandibular. A resposta da car-tilagem condilar da mandbula determinada por fatoresextrnsecos e intrnsecos. A literatura trata amplamente dasfunes orais e do metabolismo fisiolgico na cartilagem condilar.Essa cartilagem responde s foras mecnicas com crescimen-to endocondral e/ou aumentando a camada de fibrocartilagempara que esta possa suportar as cargas, protegendo, assim, acartilagem de danos. Em roedores, os movimentos da mand-bula para a frente estimulam a fisiologia da cartilagem condilar.Em humanos, os movimentos ltero-protrusivos da mandbulaso a melhor maneira de estimular respostas na articulaotemporomandibular. Portanto, a manuteno de uma funooral dinmica essencial para uma fisiologia correta da cartila-gem e, conseqentemente, uma articulao temporomandi-bular saudvel. No entanto, essa resposta pode estar relacio-nada a fatores genticos, que podem determinar a qualidadeda resposta.

PALAVRAS-CHAVE: Cartilagem condilar; Ossificaoendocondral; Funo oral; Osso que suporta a carga; Fatoresintrnsicos e extrnsicos.

1 DDS, MDSc, PhD (cursando); Biologia e Patologia Oral Faculdade de Odontologia, Universidade de Queensland, Austrlia; The University of Queensland, St. Lucia Campus, Brisbane, QLD. 4072, Australia; e-mail: [email protected] ou [email protected]

1 DDS, MDSc, PhD (in course); Oral Biology & PathologySchool of Dentistry The University of Queensland, Australia; The University of Queensland, St. Lucia Campus, Brisbane, QLD. 4072,

Australia; e-mail: [email protected]. au or germanramirez@hotmail. com

Ramirez-Yaez GO. The mandibular condylar cartilage: a review. OrtopRev Int Ortop Func 2004; 1(1):85-94.

The mandibular cartilage is a specialized structure present onthe surface of the mandibular condyles. It plays two majorfunctions, endochondral growth and joint function. This cartilageis composed by two types: a fibrocartilage which plays itsmajor role bearing the loads, and, a hyaline cartilage whichmainly participate in endochondral ossification and mandibu-lar growth. The current paper reviews the actual knowledgeabout this specialized cartilage and its relationship with thecraniomandibular function. The response of the mandibularcondylar cartilage is determined by extrinsic and intrinsicfactors. Oral function and physiological metabolism at thecondylar cartilage are widely related through the literature.

This cartilage responds to mechanical forces with endochondralgrowth and/or increasing the fibrocartilage layer to bear theloads, and so, to avoid cartilage damage. In rodents, mandi-bular forward movements stimuli the condylar cartilagephysiology. In humans, latero-protrusive movements of themandible are the best way to stimulate responses at thetemporomandibular joint. For this reason, maintenance of adynamic oral function is essential to keep a correct cartilagephysiology, and thus, a healthy temporomandibular joint.However, this response may be related with genetic factorswhich could determine the quality of the response.

KEYWORDS: Condylar cartilage; Endochondral ossification; Oralfunction; Load-bearing bone; Intrinsic and extrinsic factors.

Revista Internacional de Ortopedia Funcional / International Journal of Jaw Functional Orthopedics 2004; 1(1):85-94


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Cartilagem Condilar da Mandbula: uma RevisoThe Mandibular Condylar Cartilage: a Review


A cartilagem condilar o mais importante local decrescimento da mandbula 1,2,3. Isso no nega o importan-te papel que outras reas desempenham no crescimentomandibular, bem como sua influncia na quantidade e di-reo desse crescimento. No entanto, a cartilagemcondilar responsvel pelo comprimento final da mand-bula2. A finalidade deste trabalho rever o conhecimentoexistente sobre a fisiologia da cartilagem condilar e comoesta responde aos estmulos extrnsecos e intrnsecos.

Algumas caractersticas especficas diferenciam a carti-lagem no cndilo mandibular da cartilagem encontradana epfise dos ossos longos. Ao contrrio da cartilagemepifisria, que se desenvolve a partir do condro-skeleton , acartilagem condilar da mandbula se desenvolve a partirdas membranas sseas durante a embriognese. Nessecontexto, considera-se uma cartilagem secundria em vez

de uma cartilagem primria4,5,6

. A presena de dois tiposde cartilagem, uma fibrocartilagem na superfcie e umacartilagem hialina abaixo, permite que a cartilagem condilarse adapte melhor s foras do que as cartilagens primri-as7. A cartilagem secundria est presente nas aves, ma-mferos e em alguns pequenos vertebrados 8. Os apare-lhos ortopdicos podem modificar no apenas a direo,mas tambm a quantidade de crescimento mandibular,graas presena dessa cartilagem secundria no cndilomandibular. Nos ossos longos, a presena de uma cartila-gem primria permite somente modificar a direo docrescimento 9.

Estrutura da cartilagem condilar da mandbulaA cartilagem condilar apresenta algumas diferenas

morfolgicas e estruturais em relao cartilagem prim-ria. Estruturalmente, apresenta quatro camadas diferentes(Figura 1). A camada fibrosa compe-se principalmentede fibroblastos e colgeno tipo I. Essa camada suporta asforas transmitidas para a articulao temporomandibular(ATM) durante a funo mandibular. A camada proliferativa composta por clulas mesenquimais ou indiferenciadas.Essas clulas tm a capacidade de se diferenciar em

fibroblastos, que formam a camada fibrosa, ou emcondroblastos, isto , as clulas cartilaginosas encontradasna cartilagem hialina. A camada madura composta porcondroblastos que sintetizam a matriz cartilaginosa, prin-cipalmente o colgeno tipo II. Os condroblastos sehipertrofiam e aumentam em volume quando alcanam altima camada da cartilagem hialina, a camada hipertrfica.Essa rea conhecida como a zona de ossificaoendocondral. At o presente, no se sabe ao certo se amatriz cartilaginosa mineralizada reabsorvida e um novo

The condylar cartilage is the most importantgrowing site in the mandible 1,2,3. This does not denythat other areas play an important role in mandibulargrowth, and influence the amount and direction of that growth. However, the condylar cartilage isresponsible for the final length of the mandible 2. Thepurpose of this paper is to review the actual knowledgeabout the physiology of the mandibular condylarcartilage and how this cartilage responds to extrinsicand intrinsic stimulus.

Some specific features differentiate the cartilagefrom the mandibular condyle with that found in theepiphysis of the long bones. Unlikely epiphysiarycartilage, which develops from the chondro-skeleton,mandibular condylar cartilage develops from the bonemembranes during embryogenesis. In this context, it

is considered a secondary instead of a primarycartilage 4,5,6. The presence of two types of cartilage, afibrocartilage on the surface and a hyaline cartilageunderneath, allows the condylar cartilage to adaptbetter to forces than the primary cartilages 7. Thesecondary cartilage is present in avian, mammals andin some small vertebrates 8. Orthopedic appliancesmay modify not only the direction of the mandibulargrowth, but also the amount of mandibular growthdue to the presence of this secondary cartilage at themandibular condyle. In long bones, the presence of aprimary cartilage only permits to modify the directionof the growth 9.

The structure of the mandibularcondylar cartilage

The condylar cartilage presents somemorphological and structural differences compared tothe primary cartilage. Structurally, it presents fourdifferent layers (Figure 1). Fibrous layer is mainlycomposed by fibroblasts and collagen type I. This layerwithstand the forces transmitted in to thetemporomandibular joint (TMJ) during mandibular

function. Undifferentiated or mesenchymal cellscompose the proliferative layer. These cells have theability to differentiate either in fibroblasts going to thefibrous layer, or in chondroblasts, which are thecartilage cells found in the hyaline cartilage. The maturelayer is composed by chondroblasts synthesizingcartilage matrix, mainly collagen type II. Thechondroblasts hypertrophy and increase its volumewhen they reach the last layer of the hyaline cartilage,the hypertrophic layer. In this layer the cartilage matrix

INTRODUO / INTRODUCTION


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osso depositado, ou se atua como suporte para deposi-o ssea. Tampouco se sabe se a clula cartilaginosahipertrofiada sofre apoptose ou se permanece como umaclula diferente. Para melhor compreenso da morfologiada cartilagem mandibular, o autor recomenda a leitura dotrabalho de Luder 3,7,10 . Embora a cartilagem primria apre-sente uma estrutura semelhante, a fibrocartilagem (fun-o articular) e a cartilagem hialina (funo de crescimen-to) esto separadas por uma camada de osso trabecular(Figura 2). Portanto, o crescimento e a funo articularnos ossos longos se processam em diferentes locais doosso, ao passo que, na cartilagem mandibular, as duas fun-es se processam no mesmo local 7.

is mineralized and then resorbed and replaced by bone. This area is known as the zone of endochondralossification. Up to date, it is not totally understood if the mineralized cartilage matrix is resorbed and newbone is deposited or if it serves as scaffold for bonedeposition. It is either known if the hypertrophiedcartilage cell goes apoptosis or it stays as a differentcell. For a better understanding of the morphology of the mandibular cartilage the author recommends toread Luders work 3,7,10 Although the primary cartilagepresents similar structure, the fibrocartilage (jointfunction) and the hyaline cartilage (growth function)are separated by a layer of trabecular bone (Figure 2).

Therefore, in the long bones growth and articularfunction are performed in different sites of the bone,while in the mandibular cartilage both functions areperformed at the same site 7.

FIGURA 2: Corte da tbia de um rato Lewis tingida com Herovicis,mostrando a camada articular (A) separada da cartilagem hialina (HC) pelo osso trabecular (B) . / FI-GURE 2: Section of a Lewis rat t ibial stained with Herovicis showing the articular layer (A) separated from the hyaline cartilage (HC) by trabecular bine (B) .

FIGURA 1: Corte condilar de um rato Lewis tingido com Herovicis mostrando o osso temporal (TB), o disco (D) e a cartilagem condilar da mandbula com suas diferentes camadas: art icular (A), proliferativa (P), madura (M) e hipertrfica (H). (EO) zona da ossificao endocondral . / FIGURE 1:Condylar section of a Lewis rat stained with Herovicis showing the temporal bone (TB), the disk (D), and the mandibular condylar cartilage with its different layers: art icular (A),proliferative (P), mature (M),and hypertrophic (H). (EO) zone of endochondral ossification .

Apesar da espessura estvel das camadas condilares,estas podem variar em funo da idade e do estgio decrescimento. Por exemplo, ao nascer, o cndilo humanoapresenta uma camada hipertrfica muito espessa e a frente

da invaso vascular est quase perpendicular ao longo eixodo processo condilar 11. Por volta dos trs anos, o cndiloassume uma aparncia que lembra o formato de foice,com acentuada reduo da espessura cartilaginosa 12. Napuberdade, poder-se-ia pensar que a ossificaoendocondral na cartilagem condilar da mandbula diminu-sse, paralelamente s placas de crescimento fundidas, maso crescimento da cartilagem condilar da mandbula pare-ce continuar por longo tempo aps o corpo ter atingidosua altura total 7. No entanto, a cartilagem condilar no

Despite the stability in thickness of condylar layers,these may vary with age and stage of growth. Forexample, at birth, human condyle presents very thickhypertrophic layer, and the front of vascular invasion is

approximately perpendicular to the long axis of thecondylar process 11. Around three years after birth, itassumes a sickle-shaped appearance with a markeddecrease in cartilage thickness 12. During puberty, onewould expect that endochondral ossification in themandibular condylar cartilage would decrease inparallel with the fused growth plates. But mandibularcondylar cartilage growth seems to proceed for aconsiderable time after growth in total body heighthas ended 7. However, condylar cartilage does not


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torna-se mais poroso 19. Histologicamente, ocorre redu-o do contedo de gua na cartilagem condilar 22, aumen-tando a concentrao de proteoglicanos e ctions, e redu-zindo o pH intracelular 23. Todas essas respostas esto dire-tamente relacionadas magnitude e durao da carga. As-sim, no se recomenda uma carga prolongada sobre a ATM,pois poderia afetar a cartilagem. A carga intermitente melhor para o metabolismo fisiolgico na cartilagem 24,25.

A dieta mole foi relacionada ao aumento demalocluses nas sociedades urbanizadas 26. Estudos realiza-dos em sociedades rurais demonstraram menor incidnciade malocluses. Estas aumentam quando a populao ru-ral se transfere para a cidade. No entanto, a presena demalocluso est intimamente relacionada ao estmulo ex-terno e ao padro gentico. Esse tpico ser abordado maisdetalhadamente nas sees seguintes.

Matriz extracelular na cartilagem condilar

Conforme j descrito acima, a cartilagem condilar formada por dois tipos diferentes de cartilagem,fibrocartilagem e cartilagem hialina. O colgeno I a prin-cipal protena da fibrocartilagem, sendo encontrado tam-bm em torno das clulas hipertrficas, prximo zona deossificao endocondral. Esse colgeno resiste a cargasmultidirecionais que afetam a cartilagem da mandbula du-rante movimentos funcionais ou parafuncionais 23. Assim, afibrocartilagem suporta cargas compressivas, possibilitandoflexibilidade suficiente para adaptar-se e distribuir as cargassuavemente. Estudos realizados em nosso laboratrio de-monstraram que a alterao da relao dos incisivos emratos estimula a expresso do fator de crescimentoepidrmico (dados no publicados). Esse fator de cresci-mento um pr-requisito para a mudana fenotpica decondroblastos em clulas fibroblsticas 27. Deduz-se, por-tanto, que se forma uma camada fibrosa mais espessa parasuportar o excesso de foras transmitidas ATM, resultan-tes de uma alterao oclusal, conforme estudos realizadospor outros autores 20,28.

O colgeno tipo II a principal protena da cartila-gem hialina 29. Nessa cartilagem so encontrados tam-bm outros tipos de colgeno, tais como os tipos VI,

IX, X e XI. O colgeno VI une as clulas matriz nazona proliferativa 30. O colgeno IX atua como ligaoentre a matriz e os diferentes componentes da cartila-gem31. O colgeno X atua como suporte durante a de-gradao do colgeno II no processo de substituio dacartilagem pelo osso 30. H maior quantidade de todosos colgenos, do contedo de glicosaminoglicanos e donmero de clulas, quando a funo oral obedece a umpadro fisiolgico 30.

As protenas sseas tambm esto presentes na car-

porous 19. Histologically, there is a reduction in thecontent of water in the condylar cartilage 22, increasingthe concentration of proteoglycans and cations andreducing the intracellular pH 23. All these responsesare directly related with the magnitude and the durationof the load. Thus, prolonged loading of the TMJ is notrecommended as the cartilage can be affected.Intermittent loading is better for a physiologicalmetabolism in the cartilage 24,25 .

Soft diet has been related with an increase inmalocclusions in the urbanized societies 26. Studies inrural societies have shown a lower incidence inmalocclusions, which increase when people from therural areas move to the cities. However, there is ahigh relationship between the external stimulus andthe genetic pattern for a malocclusion to be present.

This topic is going to be further discussed on thefollowing sections.

The extracellular matrixin the condylar cartilageAs described previously, two different types of

cartilage compose the mandibular condylar cartilage,fibrocartilage and hyaline cartilage. Collagen I is themajor protein of the fibrocartilage and, it is also foundaround the hypertrophic cells near to the zone of endochondral ossification. This collagen resists themultidirectional loads affecting the mandibular cartilageduring the functional or parafunctional movements 23.

Thus, the fibrocartilage withstands the compressiveloads permiting enough flexibility to adapt to and todistribute the loads in a smooth pattern. Studies inour lab have shown that alteration of the incisorrelationship in rats stimulates epidermal growth factorexpression (unpublished data). This growth factor is aprerequisite for the phenotypic change fromchondroblasts to fibroblastic cells 27. This infers that athicker fibrous layer is formed to withstand theexcessive forces transmitted to the TMJ due to analteration in the occlusion, which correlates with studiesperformed by other authors 20,28.

Collagen type II is the major protein of the hyalinecartilage 29. Other collagen types, such as types VI, IX, X,and XI, are also found in this cartilage. Collagen VI bindsthe cells with the matrix in the proliferative zone 30.Collagen IX serves as a link between the matrix and thedifferent components of the cartilage 31. Collagen X ser-ves as scaffold during degradation of collagen II over thereplacement of cartilage by bone 30. All collagens and thecontent of glycosaminoglycans, as well as the number of cells, are increased as the oral function is performed in a


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tilagem condilar. Tanto osteopontina como osteocalcinaforam detectadas durante a biomineralizao da matrizcartilaginosa 32. Sua expresso reduz-se consideravelmen-te quando a funo oral diminui, e esse fenmeno acompanhado por uma reduo no ritmo e quantidadede deposio ssea 32. A carga reduzida sobre o cndilotambm aumenta a expresso da osteocalcina 33. Essaprotena expressa-se quando as clulas cartilaginosas es-to prontas para mineralizao. Portanto, uma mudanana funo acelera a transformao de um padrocartilaginoso em padro osteide 33. Isso confirmadopelo fato de que uma funo incisal alterada aumenta aexpresso do fator de crescimento transformador beta116, uma citocina utilizada como indicadora da maturi-dade das clulas cartilaginosas. Uma funo alterada tam-bm est ligada reduo do contedo deglicosaminoglicanos, o que aumenta o risco deosteoartrose 21,23 . Portanto, uma funo oral adequada

importante para manter o metabolismo da cartilagem eestimular a sntese da matriz 23. Os estmulos corretospodem produzir respostas fisiolgicas na cartilagemcondilar da mandbula, em qualquer estgio da vida 23.

Movimentos mandibularese crescimento mandibularDesde a lei de Wolff, a maioria dos cientistas concor-

da que a funo est intimamente relacionada ao cresci-mento mandibular. Essa questo foi abordada por Mossem toda a sua teoria sobre a matriz funcional 34,35,36,37 .Petrovic tambm demonstrou que a cartilagem condilarda mandbula recebe nutrientes, minerais e fatores de cres-cimento da zona retrodiscal quando essa zona estiradapela ao do msculo pterigide lateral, durante o movi-mento da mandbula 24,38. Copray tambm concorda comesse conceito ao afirmar que a zona posterior do cndilorecebe o estmulo gerado durante a amamentao e queesses estmulos so diretamente produzidos pela contra-o do msculo pterigide lateral 39. A dieta dura aumentaos movimentos para a frente e os movimentos laterais 26,40.O aumento dos movimentos mandibulares proporcionaum metabolismo melhor e mais fisiolgico na cartilagem

condilar, o que resulta em mais crescimentoendocondral 26,40 .No contato incisal, verifica-se a presena de carga

mxima da cartilagem 14,21,22,39,41 . Segundo relatos, o es-tmulo ideal ocorre quando o tero incisal do incisivoinferior em seu aspecto bucal toca o incisivo superioraproximadamente no tero incisal e mdio do aspectopalatino 42,43 . importante lembrar que essa uma cargadinmica e no esttica. Uma carga esttica pode pro-vocar excesso de carga na ATM, levando a uma condi-

physiological pattern 30.Bone proteins are also present in the condylar

cartilage. Osteopontin and osteocalcin have beendetected during the biomineralization of the cartilaginousmatrix 32. Their expression is significantly reduced whenthe oral function reduces and this phenomenon isaccompanied by a reduction in the rate and amount of bone deposition 32. Reduced loadings on the condylealso increase the expression of osteocalcin 33. Thisprotein is expressed when the cartilage cells are readyfor mineralization. Thus, an alteration in functionaccelerates the turnover from a cartilaginous pattern toan osteoid pattern 33. This is also supported by the factthat an altered incisal function increases the expressionof transforming growth factor-beta 1 16, a cytokine usedas a marker of cartilage cells maturity. An altered functionalso correlates with reduced content of glycosaminoglycans and this increase the risk of

osteoarthrosis21,23

. Therefore, an adequate oral functionis important to maintain cartilage metabolism and tostimulate matrix synthesis 23. Correct stimuli mayproduce physiological responses in the mandibularcondylar cartilage at any stage of life 23.

Mandibular movementsand mandibular growthSince Wolffs law, the most of the scientists agree

that function is intimately related with mandibulargrowth. Moss probed this throughout his theory aboutthe functional matrix 34,35,36,37 . Petrovic also showedthat the mandibular condylar cartilage receive nutrients,minerals and growth factors from the retro-discalzone, when this zone is stretched by the action of thelateral pterigoid muscle during the mandibularmovement 24,38 . This concept also agrees withCoprays statement, which states that the posteriorzone of the condyle receives stimulus generated duringbreast-feeding, and that these stimulus are directlyproduce by the contraction of the lateral pterigoidmuscle 39. Hard diet increases forward and lateralmovements of the mandible 26,40. An increase in man-

dibular movements permits a better and morephysiological metabolism in the condylar cartilage,which results in more endochondral growth 26,40.

Maximum load of the cartilage is present duringincisal contact 14,21,22,39,41 . The ideal stimuli has beenreported to occur when the incisal third of the lowerincisor on its buccal aspect touch the upper incisorabout the incisal and middle thirds on its palatalaspect 42,43 . It is important to keep in mind that this isa dynamic and not a static loading. A static loading


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Fatores intrnsecos e cartilagemcondilar da mandbulaSabe-se que inmeros fatores intrnsecos, tais como

hormnio do crescimento (GH), paratormnio (PTH) eprotena relacionada ao paratormnio (PTHrP), bemcomo os fatores de crescimento, influenciam o cresci-mento da cartilagem 51,52,53,54,55,56,57,58 . Nas cartilagens pri-mrias, o hormnio do crescimento tem efeito direto noritmo de diferenciao das clulas tronco emcondroblastos. Ele aumenta indiretamente a atividademittica na camada proliferativa, atravs dos efeitos dofator-1 de crescimento autcrino e parcrino, semelhan-te insulina 59,60. Assim, o crescimento da cartilagem nosossos longos, na sincondrose esfeno-occipital e na cartila-gem presente no osso esfenide e no etmide, todas con-sideradas cartilagens primrias, principalmente controla-do por fatores intrnsecos, principalmente pelo hormniodo crescimento (GH). Por outro lado, a cartilagem condilar

da mandbula, bem como a cartilagem presente na apfisecoronide, no meio da sutura palatina e no calo de cicatri-zao da fratura, respondem fortemente a fatoresextrnsecos 9. No obstante, os fatores intrnsecos tambmproduzem um efeito significativo nas cartilagens secundri-as. Segundo relatos, os fatores de crescimento e oshormnios sexuais atuam na cartilagem condilar da mand-bula2,52,57 . Relata-se tambm que alguns deles estimulam adiviso das clulas cartilaginosas, enquanto outros retardama diviso dos condroblastos. Aparentemente, a maior parte controlada pelo GH 57, mas o efeito desse hormnio so-bre a cartilagem no bem conhecido.

Um estudo recente realizado em nosso laboratrioaumentou a compreenso do efeito do GH sobre a carti-lagem condilar da mandbula 61. Em ratos transgnicos comproduo reduzida de GH (anes), foi possvel observaro que ocorre nesses animais, cujos nveis de GH dispon-vel so mais baixos em comparao a ratos normais coma mesma tendncia hereditria. Alm disso, asuplementao de GH para os animais anes permitiuobservar a resposta da cartilagem mandibular ao GH.Confirmando a expectativa, observou-se menor ndice deatividade mittica nos animais anes, ao passo que os ani-

mais tratados com GH apresentaram melhor resposta ematividade mittica, mais alta at que nos ratos normais. interessante notar que a maturao condroblstica foi ace-lerada na cartilagem mandibular dos animais anes combaixos nveis de GH e retardada na cartilagem dos ani-mais anes tratados com GH. Concluiu-se, por esses re-sultados, que o GH regula uma relao inversa entre aatividade mittica e a maturao das clulas cartilaginosas,ou seja, um aumento do GH estimula a diviso celularmas retarda a maturao condroblstica 61.

Intrinsic factors and mandibularcondylar cartilageA number of intrinsic factors, such as growth

hormone (GH), parathormone (PTH) andparathormone-related protein (PTHrP), and growthfactors, are known to influence cartilagegrowth 51,52,53,54,55,56,57,58 . In primary cartilages,growth hormone has a direct effect on thedifferentiation rate of the stem cells to chondroblasts.It increases mitotic activity in the proliferative layerindirectly through the effect of autocrine/paracrineinsulin-like growth factor-1 59,60 . Thus, cartilagegrowth in the long bones, in the spheno-occipitalsynchondrosis, and in the cartilage present in thesphenoid and etmoid bones, all of them consideredprimary cartilages, is mainly controlled by intrinsicfactors, specifically by the growth hormone (GH). Incontrast, the mandibular condylar cartilage as well

as the cartilage present in the coronoid apophisis, inthe middle palatal suture, and in the fracture healingcallus highly respond to extrinsic factors 9.Nevertheless, intrinsic factors also produce asignificant effect in the secondary cartilages. Growthfactors and sexual hormones have been reported toact on the mandibular condylar cartilage 2,52,57 . Someof them are reported to stimulate cartilage cell divisionand others to delay chondroblasts division. It seemsthat the most of them are controlled by the GH 57,but the effect of this hormone on the cartilage is notwell understood.

A recent study performed in our laboratory hasproduced insights about the effect of the GH on themandibular condylar cartilage 61. By means of transgenicrats with a reduced production of GH (dwarfs), it waspossible to observe what occurs in those animals wherelower levels of GH are available, comparing withnormal rats from the same strain. In addition, GHsupplementation to the dwarf animals permitted toobserve the response of the mandibular cartilage toGH. As expected, a lower rate in mitotic activity isobserved in the dwarf animals, whereas those animals

treated with GH showed a high response in mitoticactivity, even higher than the normal rats. Interestingly,chondroblasts maturation was accelerated in the man-dibular cartilage of those dwarf animals with low levelsof GH, and delayed in the cartilage of those dwarf animals treated with GH. It is concluded from theseresults that GH regulates an inverse relationshipbetween mitotic activity and cartilage cells maturation,where, an increase in GH stimulates cell division whileretards chondroblasts maturation 61.


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Examinando-se a literatura e analisando os resultadosdos nossos estudos recentes, nota-se que a cartilagemcondilar da mandbula afetada tanto por fatoresextrnsecos, como funo, por exemplo, quanto por fa-tores intrnsecos, como os hormnios e fatores de cres-cimento. O GH, em particular, produz um aumento daatividade mittica das clulas cartilaginosas, mas retarda amaturao dessas clulas 61. Em outras palavras, existemmais condroblastos novos e indiferenciados disponveisna cartilagem mandibular devido ao do GH. Por ou-tro lado, as cargas compressivas aceleram a maturaodos condroblastos e estimulam a sntese dos fatores decrescimento e dos marcadores sseos 16,50, o que significaque a ossificao endocondral estimulada. Portanto, tantoos fatores intrnsecos como os extrnsecos so necessri-os para produzir a ossificao endocondral. O GH e pos-

sivelmente outros hormnios seriam necessrios paraproduzir mais clulas cartilaginosas na cartilagem mandi-bular, ao passo que a funo oral s seria necessria comoestmulo para diferenciar e sintetizar a matriz cartilaginosa,permitindo a formao do osso endocondral e, conse-qentemente, o crescimento mandibular. Esse conceito importante para os Clnicos no apenas pela boa res-posta ao estmulo da funo oral para obter crescimentomandibular. A qualidade da resposta tambm depende dosnveis hormonais 9,61,62,63 , principalmente do GH, produ-zidos pelo paciente. Hoje sabemos claramente que a fun-o oral um fator chave para o crescimento mandibu-lar42,43,44 . No entanto, o papel dos fatores intrnsecosdemanda uma investigao mais profunda, para que sepossa desenvolver ferramentas que permitam identificar,com preciso e diretamente no paciente, a qualidade daresposta.

CONCLUSES / CONCLUSIONS

REFERNCIAS / REFERENCES1. Hinton RJ. Form and function in the temporomandibular joint. In: Carlson DS (ed).Craniofacial biology. Ann Arbor: University of Michigan, Center for Human Growth andDevelopment; 1981. p.37-60. Monograph N o10.2. Petrovic AG, Stutzmann JJ, Gasson N. The final length of the mandible: is itgenetically predetermined? In: Carlson DS (ed). Craniofacial biology. Ann Arbor:

University of Michigan, Center for Human Growth and Development; 1981. p.105-26.Monograph N o10.3. Luder HU. Age changes in the articular tissue of human mandibular condyles fromadolescence to old age: a semiquantitative light microscopic study. Anat Rec 1998;251(4):439-47.4. Durkin JF. Secondary cartilage: a misnomer? Am J Orthod 1972; 62(1):15-41.5. Goret-Nicaise M, Lengele B, Dhem A. The function of Meckels and secondarycartilages in the histomorphogenesis of the cat mandibular symphysis. Arch AnatMicrosc Morphol Exp 1984; 73(4):291-303.6. Hall BK. Genetic and epigenetic control of connective tissues in the craniofacialstructures. Birth Defects Orig Artic Ser 1984; 20(3):1-17.7. Luder HU. Posnatal development, aging, and degeneration of the temporomandibular

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Throughout the literature and analyzing the resultsfrom our recent studies, the mandibular condylarcartilage is affected as by extrinsic factors, e.g. function,as by intrinsic factors, e.g. hormones and growthfactors. Particularly GH produces an increase in themitotic activity of the cartilage cells but delay thematuration of these cells 61. In other words, moreundifferentiated and new chondroblasts are availablein the mandibular cartilage because the action of GH.On the other hand, compressive loads accelerateschondroblasts maturation and stimulates the synthesisof growth factors and bone markers 16,50, which means,the endochondral ossification is stimulated. Therefore,both intrinsic and extrinsic factors are necessary forendochondral ossification occurring. GH and possiblyother hormones would be required to produce more

cartilage cells in the mandibular cartilage, while oralfunction would be required to stimulate these cells todifferentiate and synthesize cartilage matrix, whichpermits endochondral bone formation, therefore,mandibular growth. This concept is important for theClinician because not only a good response will beobtained stimulating oral function in order to obtainmandibular growth. The quality of the response alsodepends on the levels of hormones 9,61,62,63 , particularlyGH, produced by the patient. Up to date is clear thatoral function is a key factor for mandibulargrowing42,43,44 . However, the role of intrinsic factorsneeds to be further investigated in order to developtools which accurately permit to identify directly onthe patient, the quality of the response.


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Recebido para publicao em / Received for publication on : 20/01/04Enviado para anlise em / Submitted to analysis on : 18/02/04

Aceito para publicao em / Accepted for publication on : 10/03/04

revisao cartilagem

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