Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MANDIBULAR CONDYLE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources
PubMed2003

[Clinical significance of the Krogh-Poulsen bite test in mandibular dysfunction].

INTRODUCTION: The bite test was initially described as the Krogh-Poulsen test consists of biting a flat and thin wedge placed unilaterally between the molars. Temporomandibular joint (TMJ) pain located on the ipsilateral side is considered as muscular, when on the contralateral side pain signifies a joint problem. Although this test is widely used, no scientific evaluation of its real clinical value has been published. MATERIAL AND METHOD: A prospective study is conducted in 32 patients exhibiting temporomandibular pain (n=40) at the bite test. The results of the bite test were compared with results of computed tomography of the TMJ. Several criteria are studied: joint space narrowing, retrusion of the mandibular condyle in occlusal position, bony signs of joint degeneration. Chi-square and Student's t test were used for statistical analysis of correlations between clinical findings and radiological abnormalities. RESULTS: Significant results demonstrated a high degree of radiologically detectable disorders in patients with joint pain as defined by the bite test. All of these patients presented at least one radiological sign of joint disease. There was also a low degree of radiologically detected joint disturbance in patients with muscular pain according to the bite test, 70% of them presenting no radiological abnormality. DISCUSSION: It is concluded that the bite test is of significant value for evaluation of TMJ disorders and can be useful for the indication of complementary radiological examinations.

Adolescent↗
PubMed1995

An immunohistochemical study of the effects of surgical induction of anterior disc displacement in the rabbit craniomandibular joint on type I and type II collagens.

The right craniomandibular joint (CMJ) was exposed surgically and all the discal attachments severed except for the posterior one. The disc was then repositioned anteriorly and sutured to the zygomatic arch. The left joint served as a sham-operated control; 10 other joints were used as non-operated controls. Deeply anaesthetized rabbits were perfused with 2% buffered formalin 2 weeks (10 rabbits) or 6 weeks (10 rabbits) after the induction of the anterior disc displacement (ADD). The articular disc, bilaminar zone, mandibular condyle and articular eminence were excised. The condyles and the articular eminences were demineralized in EDTA. All tissues were then sectioned at 10 microns in a cryostat. Sections were incubated with polyclonal antibodies directed against type I or type II collagens. Following incubation in the appropriate fluorescein isothiocyanate-labelled secondary antibodies, these specimens were studied under the fluorescence microscope. At 2 weeks there was a reduction in type II collagen immunostaining; some areas of the experimental condylar cartilage showed a switch from type II to type I collagen. However, at 6 weeks there was an increase in type II collagen immunostaining and a decrease in type I compared to the 2-week group. It is concluded that surgical induction of ADD in the rabbit CMJ leads to alteration in the condylar cartilage collagen phenotype similar to that reported for osteoarthritic cartilage of other synovial joints.

Animals↗
PubMed2006

Effects of estrogen on chondrocyte proliferation and collagen synthesis in skeletally mature articular cartilage.

PURPOSE: Estrogen has been shown to have a modulating effect on cartilage thickness. This investigation was performed to determine the effects of estrogen supplementation on cartilage thickness, cellular proliferation, and type II and X collagen production in skeletally mature rat cartilage, both in an organ culture and cell culture system. MATERIALS AND METHODS: Mandibular condyles were harvested from 8-week-old female Sprague Dawley rats and placed into tissue culture plates containing culture media with or without 17beta-estradiol supplementation. Organ cultures were labeled with 5-bromo-2'-deoxyuridine on culture day 2 or 4 to determine the effects of estrogen supplementation on the cellular mitotic index. Histomorphometric analysis of the organ culture sections was used to determine the thickness (microm) of the various cartilage zones, as well as the total cartilage thickness following estrogen exposure. Type X collagen was immunohistochemically identified in the ECM of hypertrophic chondrocytes using a rabbit anti-rat collagen type X antibody raised against the NCl domain. The reaction was visualized with an avidin-biotin peroxidase detection system (Vector Laboratories, Burlingame, CA). In a separate experiment, articulating cartilage chondrocytes were harvested by collagenase digestion and cultured at 5 x 10(5) cells per 35 mm tissue culture plate. Second subculture chondrocytes were divided into 2 groups: controls and [10(-8) M] 17beta-estradiol (E(2)-10(-8) M) and grown to confluence. The cell cultures were used to establish growth curves for each group using cell counts at 2-day intervals. RESULTS: In the organ culture experiment, 17beta-estradiol-treated condyles had a significant decrease in total cartilage thickness after 4 days in culture (P < .05). Estrogen supplementation resulted in a significant reduction in the mitotic index as early as culture day 2 (P < .05). Type X collagen deposition into the extracellular matrix was visibly increased in the hypertrophic chondrocyte zone for the estrogen-supplemented group on experimental days 2 and 4 compared with the control group. In the cell culture system, 17beta-estradiol [10(-8) M] decreased chondrocyte proliferation during logarithmic growth (P < .05) and at confluence (P < .05). CONCLUSION: These data show that estrogen decreased cartilage thickness by inhibition of chondrocyte proliferation and increased chondrocyte maturation. These observed effects showed the potential role of estrogen in the modulation of skeletally mature cartilage.

Animals↗
PubMed2002

A three-dimensional method of visualizing the temporomandibular joint based on magnetic resonance imaging in a case of juvenile chronic arthritis.

AIM: The purpose of this study was to present a new visualizing method for temporomandibular joint (TMJ) pathology in 3D at several condylar positions and to apply the method to a case of juvenile chronic arthritis (JCA) with previously diagnosed bilateral TMJ disorder and to a subject without signs and symptoms from the TMJ. SUBJECT: The 20-year-old female patient had suffered from polyarticular JCA from the age of 6 years 8 months. The present study is based on a follow-up examination after the completion of orthodontic treatment with the Herbst appliance. Both TMJs were examined using magnetic resonance imaging (MRI) at closed and open mouth positions. The mandibular condyle, the glenoid fossa and the articular disc were segmented and 3D reconstruction of these structures was carried out. RESULTS: The condyle was characterized by an increased sagittal diameter with osteophyte-like formation at the anterior aspect of the condylar head and flattening of the superior surface. The depth of the glenoid fossa was reduced and the articular eminence was remarkably flat. The articular disc was markedly diminished and posteriorly placed on the condylar head. The distance of the condylar path during mouth opening was reduced and the curvature of the condylar path was quite flat. The disc moved slightly posteriorly on the condylar head and remained in the glenoid fossa during mouth opening. CONCLUSION: The imaging modality described improves visualization of TMJ morphology and gains insight into the TMJ pathology of the JCA patient, adding to understanding of the clinical problems.

Adult↗
PubMed1986

Further characterization of spontaneous arthritic changes in murine squamo-mandibular joint: histopathological aspects.

The appearance of age-related ulcerative changes in the mouse mandibular condyle were evaluated by light and electron microscopy examinations. Fibrillations appeared along the articular surface and in deeper tissue regions, as early as at six months of age. Such changes were characterized by a marked loss of the tissue's cellularity and by a marked reduction in matrix metachromasia and safranin-0 staining. These microscopical changes were accompanied by a reduced reactivity for both ruthenium red and colloidal iron binding, as noted ultrastructurally. At the same time, increasing numbers of erythrocytes appeared to be adhered to the surface irregularities and were also found in deeper regions within the articular lesions. Using morphological criteria, it became apparent that the degenerative changes of aging articular cartilage started at the more superficial regions of the tissue and only thereafter proceeded toward the chondro-osseous junction. Also, with the advancement of age, the degenerative changes became more severe.

Aging↗
PubMed1996

An immunohistochemical study of collagen types III, VI and IX in rabbit craniomandibular joint tissues following surgical induction of anterior disk displacement.

The purpose of this study was to determine the effect of surgical induction of anterior disk displacement (ADD) on type-III, VI and IX collagens of the rabbit craniomandibular joint (CMJ) tissues using an immunohistochemical technique. The right joint was exposed surgically, all discal attachments were severed except for the posterior discal attachment (bilaminar zone). The disk was then repositioned anteriorly and sutured to the zygomatic arch. The left joint served as a sham-operated control. Ten additional joints were used as non-operated controls. Deeply anesthetized rabbits were perfused with 2% buffered formalin 2 weeks (10 rabbits) or 6 weeks (10 rabbits) following surgery. The articular disk, bilaminar zone, mandibular condyle and articular eminence were excised. The last two were decalcified in EDTA. All tissues were then sectioned at 10 microns in a cryostat. Sections were incubated with monoclonal antibodies directed against type-III, VI or IX collagens. Following incubation in the appropriate FITC-labelled secondary antibodies, all sections were studied under the fluorescence microscope. The results showed a reduction in immunostaining for type-VI and IX collagens in the condylar cartilage, disk and articular eminence at 2 weeks, followed by an increase in their immunostaining at 6 weeks and the appearance of a de novo type-III collagen in the condylar cartilage and the articular eminence. It is concluded that surgical induction of ADD in the rabbit CMJ leads to alterations in its type-III, VI and IX collagens.

Animals↗
PubMed2006

Structural and mechanical properties of mandibular condylar bone.

The trabecular bone of the mandibular condyle is structurally anisotropic and heterogeneous. We hypothesized that its apparent elastic moduli are also anisotropic and heterogeneous, and depend on trabecular density and orientation. Eleven condyles were scanned with a micro-CT system. Volumes of interest were selected for the construction of finite element models. We simulated compressive and shear tests to determine the principal mechanical directions and the apparent elastic moduli. Compressive moduli were relatively large in directions acting in the sagittal plane, and small in the mediolateral direction. The degree of mechanical anisotropy ranged from 4.7 to 10.8. Shear moduli were largest in the sagittal plane and smallest in the transverse plane. The magnitudes of the moduli varied with the condylar region and were proportional to the bone volume fraction. Furthermore, principal mechanical direction correlated significantly with principal structural direction. It was concluded that variation in trabecular structure coincides with variation in apparent mechanical properties.

Aged↗
PubMed2000

Alterations in the periodontium after ovariectomy in rats: the effects of a Japanese herbal medicine, Chujo-to.

Ovariectomy-induced changes on the periodontium (gingiva, alveolar bone, and periodontal ligament) in rats and the preventive effects of a Japanese herbal medicine, Chujo-to, were studied for a period of 49 days. The rats were divided into five groups: sham-operated (sham), ovariectomized (OVX), OVX given Chujo-to, OVX given 17beta-oestradiol, and OVX given the vehicle for 17beta-oestradiol, respectively. After the test period, the bone mineral content (BMC) of the mandibular condyle in OVX rats was similar to those in both sham rats and the OVX rats treated with either Chujo-to or 17beta-oestradiol. However, the scanning electron microscopic (SEM) analyses revealed that the periodontal ligament of the OVX rats and the OVX rats treated with Chujo-to became more coarse than that of the sham rats or the rats treated with 17beta-oestradiol. The surface of the alveolar bone in the OVX rats appeared to contain numerous small granules, which were not present in the sham rats and the rats treated with either Chujo-to or 17beta-oestradiol. These results suggest that ovariectomy caused alterations in the peridontium, but Chujo-to had a preventive effect on the surface architecture of the alveolar bones.

Alveolar Bone Loss↗
PubMed2004

The interpositional dermis-fat graft in the management of temporomandibular joint ankylosis.

The aim of this retrospective clinical study is to present the clinical experience of using dermis-fat interpositional grafts in the surgical management of temporomandibular joint (TMJ) ankylosis in adult patients. Eleven adult patients who presented with ankylosis of the TMJ were identified and included in the study. All patients underwent a TMJ gap arthroplasty which involved the removal of a segment of bone and fibrous tissue between the glenoid fossa and neck of the mandibular condyle. The resultant gap was filled with an autogenous dermis-fat graft procured from the patient's groin. All patients were followed up for a minimum of 2 years. Five of the 11 patients were found to have osseous ankylosis while 6 patients had fibro-osseous ankylosis. Two patients had bilateral TMJ ankylosis that were also treated with costochondral grafts which were overlaid with dermis-fat graft. The average interincisal opening was 15.6 mm on presentation which improved to an average of 35.7 mm following surgery. Patients were followed up from 2 to 6 years post-operatively (mean 41.5 months) with only 1 re-ankylosis identified out of the 13 joints treated. This study found that the use of the autogenous dermis-fat interpositional graft is an effective procedure for the prevention of re-ankylosis up to 6 years following the surgical release of TMJ ankylosis.

Adipose Tissue↗
PubMed2003

Experimental induction of anterior disk displacement of the rabbit craniomandibular joint: an immuno-electron microscopic study of collagen and proteoglycan occurrence in the condylar cartilage.

BACKGROUND: Results from our previous studies suggest that surgical induction of anterior disk displacement (ADD) in the rabbit craniomandibular joint (CMJ) leads to histopathological alterations consistent with osteoarthritis. In addition, molecular changes in collagens and glycosaminoglycans (GAGs) were observed using immunohistochemistry. The purpose of the present study was to further characterize those molecular changes in collagens and GAGs using immuno-electron microscopy. METHODS: The right joint of 15 rabbits was exposed surgically and all discal attachments were cut except for the posterior attachment (the bilaminar zone). The disc was then repositioned anteriorly and sutured to the zygomatic arch. The left joint was used as a sham-operated control. Ten additional joints were used as non-operated controls. Mandibular condyles were removed 2 weeks following surgery and processed for light and immuno-electron microscopy using colloidal gold-labeled antibodies against collagen type I, II, VI and IX and against keratan sulfate, chondroitin-4 and -6-sulfate, and link protein. RESULTS: Light microscopic results showed osteoarthritic changes. Immuno-electron microscopy of osteoarthritic cartilage demonstrated a decline in type II collagen, the abnormal presence of type I collagen and loss of type VI and IX collagens. Quantitative colloidal gold immuno-electron microscopy confirmed the depletion of keratan sulfate, chondroitin-4 and -6-sulfate, and link protein in osteoarthritic cartilage. CONCLUSION: Anterior disk displacement leads to molecular alterations in both the collagen and the proteoglycans of rabbit condylar cartilage characteristic of osteoarthritis in other synovial joints. These alterations are consistent with loss of the shock absorber function of the cartilage and injury of the underlying bone.

Animals↗
PubMed1996

Effect of reduced articular function on deposition of type I and type II collagens in the mandibular condylar cartilage of the rat.

A group of rats was fed a soft diet after weaning and the incisors shortened regularly to keep them out of occlusion. The controls were fed a hard diet. Immunohistochemical techniques and image analysis were employed to investigate deposition of pro-type I collagen and type II collagen, and the thickness of articular cartilage layers in the mandibular condyle. The immunostaining against pro-type I collagen was most intense intracellularly in the fibrous and upper chondroblast layers in 30- and 50-day-old rats fed a hard diet. In the rats fed a soft diet, marked intra- and extracellular staining against pro-type I collagen was visible in the upper chondroblast and upper hypertrophic layers but also in the lower hypertrophic layer. The intensity of staining against type II collagen was weak in animals on a soft diet, while in the animals fed a hard diet the staining was intense in the superior layers of mature chondroblasts. The total number of chondroblasts recorded was reduced by 35 percent at the age of 50 days in the soft-diet compared to the hard-diet animals. The results show that the deposition of type I and II collagens, the thickness of the cartilage cell layers and the number of chondrocytes are sensitive to alterations in loading.

Animals↗
PubMed1993

Autoradiographic study of the effects of pulsed electromagnetic fields on bone and cartilage growth in juvenile rats.

Application of pulsed electromagnetic fields (PEMF) has been used in growth and repair of non-union bone fractures. The similarities between the fibrocartilage callus in non-union bone fractures and the secondary cartilage in the mandibular condyle, both histologically and functionally, lead naturally to study the effects of PEMFs on growth in the condyle. The purposes of this study were: (1) to describe the effects of PEMFs on the growth of the condyle using autoradiography, [3H]-proline and [3H]-thymidine, and (2) to differentiate between the effects of the magnetic and electrical components of the field. Male pre-adolescent Sprague-Dawley rats (28 days old) were divided into three experimental groups of five animals each: (1) PEMF-magnetic (M), (2) PEMF-electrical (E) and (3) control, and were examined at three different times-3, 7 and 14 days of exposure. Each animal was exposed to the field for 8 h per day. Histological coronal sections were processed for quantitative autoradiography to determine the mitotic activity of the condylar cartilage and the amount of bone deposition. The PEMF (magnetic or electrical) had statistically significant effects only on the thickness of the articular zone, with the thickness in the PEMF-M group being the most reduced. Length of treatment was associated with predictable significant changes in the thickness of the condylar cartilage zones and the amount of bone deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Regenerating marrow induces systemic increase in osteo- and chondrogenesis.

Marrow ablation in long bones induces an increase in osteogenesis in distant skeletal sites. To test the role of marrow regeneration in this phenomenon, rat mandibular condyles were evaluated histomorphometrically during postablation healing of tibial marrow and after inhibition of healing. Ten days after removal of tibial marrow all bone formation parameters in the condylar subchondral bone were markedly elevated, indicating an enhanced osteoblastic activity. The thickness of the cartilaginous zone of calcification was also augmented. These changes were absent when postablation healing was inhibited in the tibia and after massive liver injury. Extensive periosteal injury induced only a slight increase in osteoblast activity. Except for a fall on day 7, the [methyl-3H]thymidine labeling index in the condylar cartilage and oral mucosa remained at control levels 3-18 days after ablation. These findings imply that stimulation of cell proliferation has only a secondary role in the skeletal response to marrow ablation. It is concluded that the systemic increase in osteogenesis occurs preferentially during marrow regeneration and is not a nonspecific skeletal reaction to tissue injury. Apparently, the systemic osteogenic response is mediated by circulating factors produced by the healing marrow; conceptually it is related to other instances where local repair in extraskeletal sites is accompanied by generalized alterations in respective tissues.

Animals↗
PubMed1983

Relationships between mandibular joint size and craniofacial size in human groups.

Substantial evidence attests to the capability of the joint to undergo morphological alteration in response to biomechanical forces transmitted to it during function. Measurements expressing the size of mandibular condyles and fossae were obtained from skulls representative of a broad spectrum of subsistence practices and tooth use. Craniofacial dimensions were measured for some groups. Considerable differences in joint size were noted between groups roughly consistent with known or presumed intensity of masticatory stress. Size was largest in the hunter-gatherers, intermediate in aboriginal horticulturalists and smallest in 20th century American caucasoids and 17th century British. In each group, male joint size was absolutely larger than females. With the exception of condylar breadth, male joint dimensions were not relatively larger than female when corrected for differences in craniofacial size. In contrast, same-sex comparisons of Eskimo and American caucasoid means adjusted for differences in craniofacial size showed joint size in Eskimos to be significantly larger, both absolutely and relatively. Eskimo females had relatively larger joints than American caucasoid males. Thus, intergroup differences in joint size persist even when differences in craniofacial size are taken into account. Although the influence of genetic factors cannot be excluded, differences in the nature or intensity of tooth use during growth may account, at least in part, for the observed differences in joint size.

Adult↗
PubMed1998

Effect of cytochalasin D on articular cartilage cell phenotype and shape in long-term organ culture.

It has been documented, on the basis of cell culture experiments, that cytochalasin treatment promotes a round cell shape in chondroblast cultures by altering the cytoskeleton, and that it simultaneously alters the balance between production of type I and type II collagens. The aim in this study was to monitor the deposition of pro-type-I and type II collagens, and possible changes in articular cartilage layers in the mandibular condyle of the mouse under the influence of Cytochalasin D (CD) when total craniomandibular joints of 5-day-old mice were cultured in one block. The experimental group comprised 20 Balb/c mice of both sexes. Twenty in vitro controls were cultured without the administration of cytochalasin. The mice in the third group were used as in vivo controls. The cells in the prechondroblast layer responded with a rapid change in shape when treated with CD and assumed a rounded morphology. The total thickness of the cell layer was reduced at 7 days. Immunostaining against pro-type-I collagen was intense in the narrow fibrous and prechondroblast layers in the CD-treated group, whereas the stained area was wider and the staining gradually reduced in the deeper cartilage layers in the in vitro controls. Staining against type II collagen became weaker at the end of the culturing period of the CD-treated group, whereas in the in vitro controls the staining against type II collagen was clearly visible at all observation times. These phenomena can be explained by changes in differentiation and the altered cell cycle of the chondroblasts in organ culture under the influence of CD.

Analysis of Variance↗
PubMed2006

Variations in mineralization affect the stress and strain distributions in cortical and trabecular bone.

The mechanical properties of bone depend largely on its degree and distribution of mineralization. The present study analyzes the effect of an inhomogeneous distribution of mineralization on the stress and strain distributions in the human mandibular condyle during static clenching. A condyle was scanned with a micro-CT scanner to create a finite element model. For every voxel the degree of mineralization (DMB) was determined from the micro-CT scan. The Young's moduli of the elements were calculated from the DMB using constant, linear, and cubic relations, respectively. Stresses, strains, and displacements in cortical and trabecular bone, as well as the condylar deformation (extension along the antero-posterion axis) and compliance were compared. Over 90% of the bone mineral was located in the cortical bone. The DMB showed large variations in both cortical bone (mean: 884, SD: 111 mg/cm(3)) and trabecular bone (mean: 738, SD: 101 mg/cm(3)). Variations of the stresses and the strains were small in cortical bone, but large in trabecular bone. In the cortical bone an inhomogeneous mineral distribution increased the stresses and the strains. In the trabecular bone, however, it decreased the stresses and increased the strains. Furthermore, the condylar compliance remained relatively constant, but the condylar deformation doubled. It was concluded that neglect of the inhomogeneity of the mineral distribution results in a large underestimation of the stresses and strains of possibly more than 50%. The stiffness of trabecular bone strongly influences the condylar deformation. Vice versa, the condylar deformation largely determines the magnitude of the strains in the trabecular bone.

Anisotropy↗
PubMed1986

A tissue culture system supporting cartilage cell differentiation, extracellular mineralization, and subsequent bone formation, using mouse condylar progenitor cells.

Undifferentiated progenitor cells of mandibular condyles of neonatal mice were kept in a tissue culture system for up to 9 days. After 2 days in culture, new chondroblasts developed within the explants, whereas the peripheries of the latter were occupied by undifferentiated cells undergoing mitosis. By 4 days in culture, many of the cartilage cells showed signs of hypertrophy, while the matrix revealed positive reactivity for type II collagen and matrix metachromasia. The process of maturation of cartilage cells appeared to have reached its final stages after 6 days in culture, at a time when the initial loci of matrix mineralization could be easily identified. Concomitantly, peripheral areas bordering the cartilaginous core, as well as portions of the cartilage, reacted positively for type I collagen and fibronectin. Light microscopy examination showed signs of new bone formation after 9 days in culture. The extracellular matrix at the upper portion of the explant, facing the medium-air interface, reacted intensely with antibodies against type I collagen and fibronectin, but not with antibodies against type II collagen. Further, the newly formed osteoid was found to have undergone mineralization, thus forming an expanded layer of new bony tissue. A close spatial association was found between mature, mineralized cartilage and new bone. Hence, we hereby introduce a new in vitro system serving as an experimental model for studies related to the differentiation of progenitor cells into chondroblasts, which in turn promote ossification.

Animals↗
PubMed2003

PTH ameliorates acidosis-induced adverse effects in skeletal growth centers: the PTH-IGF-I axis.

BACKGROUND: Chronic metabolic acidosis (CMA) exerts profound adverse effects on bone metabolism thereby leading to impaired skeletal linear growth. We have recently shown that CMA in vitro causes distinct morphological changes in skeletal growth centers along with inhibition of endochondral differentiation. In addition, CMA causes an end organ resistance to the anabolic effects of growth hormone (GH) and locally produced insulin-like growth factor-I (IGF-I) in skeletal growth centers. Given the effects of parathyroid hormone (PTH) and PTH related protein (PTHrP) on the development of cartilaginous bone, we sought to determine whether PTH has any effects on the changes induced by CMA in skeletal growth centers. The interaction between PTH and IGF-I in growth centers during neutral or acidic conditions were studied specifically. METHODS: An in vitro organ culture system using the murine mandibular condyle was employed as a model for endochondral active growth center. Condyles from six-day-old mice were cultured in BGJb medium of either neutral pH (pH approximately 7.4) or acidic pH (pH approximately 7.15) in the presence or absence of 10-10 mol/L [1-34] PTH. After 24, 48, 72 and 96 hours of culture, the condyles were washed, fixed in formaldehyde, and processed for paraffin embedding. Histologic markers of the growth center were assessed. In addition, the protein level and mRNA expression for various markers of cartilage differentiation were evaluated by immunohistochemistry and in situ hybridization, respectively. The abundance and expression levels of IGF-I and IGF-I receptor (IGF-I-R) were assessed also. RESULTS: Following incubation for 72 hours in acidic conditions, there was a marked attenuation of the chondroblastic zone, suggesting a defect in the process of cellular differentiation. Acidosis also down-regulated endochondral differentiation markers (cartilage specific proteoglycans, collagen type II). This was accompanied by a reduction in the expression of IGF-1, IGF-1 receptor and PTH receptors. PTH (10-10 mol/L) added to acidic cultures prevented the adverse effects of CMA on endochondral differentiation and increased the overall condylar growth, when compared to acidic conditions without PTH. PTH also up-regulated its own receptor in control as well as during acidic conditions, and increased the expression levels of IGF-1 and IGF-1 receptor in the acidotic condyle. Acidosis increased the expression of IGF-I binding protein-4 (IGFBP-4, an inhibitor of IGF-I activity), whereas coincubation with PTH during acidic conditions abrogated the up-regulation of IGFBP-4. Addition of a neutralizing antibody to IGF-I-R during PTH treatment under acidic conditions resulted in the abrogation of the ameliorative effect of PTH on endochondral differentiation. The protein kinase C (PKC) signaling pathway was modulated negatively by CMA. However, PTH activated PKC-alpha under both control and acidic conditions. The phorbol ester, PMA (phorbol 12-myristate 13-acetate), a PKC activator, mimicked the effect of PTH on chondrocyte differentiation. CONCLUSION: Parathyroid hormone at low concentration stimulates the differentiation and proliferation of cartilage cells and prevents the suppressive effect of acidosis on endochondral bone differentiation and on the IGF-I/IGF-I-R system in skeletal growth centers. Increased local production of IGF-I by PTH, which takes place even during acidotic conditions, mediates, at least in part, the ameliorative effect of PTH. Protein kinase C is probably one of the signaling pathways mediating the salutary effects of PTH on chondrocyte differentiation in growth centers. This study lends further credence to the notion that under certain conditions, PTH or PTHrP can exert anabolic effects in the skeleton. These findings may be of clinical-therapeutic significance in children and patients with CMA.

Acidosis↗