Activation of Transforming Growth Factor β in Chondrocytes Undergoing Endochondral Ossification

D’Angelo, Marina; Sarment, David P.; Billings, Paul C.; Pacifici, Maurizio

doi:10.1359/jbmr.2001.16.12.2339

Cited by 57 publications

(48 citation statements)

References 60 publications

(194 reference statements)

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“…Extracellular matrix-bound TGF␤ are normally stored in latent forms and can be released and activated by various serine proteases and MMPs, including MMP-9 and MMP-13 (30,31). We found that ACLtransected OA joints released elevated amounts of active TGF␤ in organ cultures, while ALN treatment suppressed the release of TGF␤ toward control levels.…”

Section: Discussionmentioning

confidence: 74%

“…In the medial tibial plateaus from ACL-transected joints, loss of proteoglycan was observed at 2 weeks postsurgery (Figures 8a and 9a). Two metalloproteinases, MMP-9 and MMP-13, have been implicated in the proteolytic activation of latent TGF␤ in cartilage tissue (29)(30)(31). As shown in Figure 8, activated TGF␤ (blue) was found in the proximity of MMP-9 (brown) (Figure 8b) in the articular cartilage of ACL-transected joints.…”

Section: Aln Blocking Of the Recruitment Of Trappositive Cells To Ostmentioning

confidence: 99%

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The role of subchondral bone remodeling in osteoarthritis: Reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model

Hayami

Pickarski

Wesolowski

et al. 2004

Arthritis & Rheumatism

510

466

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Objective. It has been suggested that subchondral bone remodeling plays a role in the progression of osteoarthritis (OA). To test this hypothesis, we characterized the changes in the rat anterior cruciate ligament transection (ACLT) model of OA and evaluated the effects of alendronate (ALN), a potent inhibitor of bone resorption, on cartilage degradation and on osteophyte formation.Methods. Male Sprague-Dawley rats underwent ACLT or sham operation of the right knee. Animals were then treated with ALN (0.03 and 0.24 g/kg/week subcutaneously) and necropsied at 2 or 10 weeks postsurgery. OA changes were evaluated. Subchondral bone volume and osteophyte area were measured by histomorphometric analysis. Coimmunostaining for transforming growth factor ␤ (TGF␤), matrix metalloproteinase 9 (MMP-9), and MMP-13 was performed to investigate the effect of ALN on local activation of TGF␤.Results. ALN was chondroprotective at both dosages, as determined by histologic criteria and collagen degradation markers. ALN suppressed subchondral bone resorption, which was markedly increased 2 weeks postsurgery, and prevented the subsequent increase in bone formation 10 weeks postsurgery, in the untreated tibial plateau of ACLT joints. Furthermore, ALN reduced the incidence and area of osteophytes in a dosedependent manner. ALN also inhibited vascular invasion into the calcified cartilage in rats with OA and blocked osteoclast recruitment to subchondral bone and osteophytes. ALN treatment reduced the local release of active TGF␤, possibly via inhibition of MMP-13 expression in articular cartilage and MMP-9 expression in subchondral bone. Conclusion. Subchondral bone remodeling plays an important role in the pathogenesis of OA. ALN or other inhibitors of bone resorption could potentially be used as disease-modifying agents in the treatment of OA.Osteoarthritis (OA) is a degenerative joint disease characterized by pain, cartilage loss, and joint stiffness. Although OA has long been considered to be primarily a cartilage disorder associated with focal articular cartilage degradation, this disease is accompanied by well-defined changes in the subchondral and periarticular bone, including sclerosis and cyst and osteophyte formation (1). The importance of the bone changes in the initiation and progression of OA is still being debated. It has been suggested that increased subchondral bone stiffness reduces the ability to dissipate the load and distribute the strain generated within the joint. This increases peak dynamic forces in the overlying articular cartilage and can accelerate its damage over time (2). The functional integrity of the articular cartilage can therefore depend on the mechanical properties of the underlying bone. Accordingly, cartilage damage leads to full-thickness cartilage loss only upon repetitive loading over an already stiffened subchondral bone plate (3).Recent studies have demonstrated increased subchondral bone turnover accompanied by specific architectural changes in the subchondral trabecular bone in OA joints (4,5...

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Section: Discussionmentioning

confidence: 74%

Section: Aln Blocking Of the Recruitment Of Trappositive Cells To Ostmentioning

confidence: 99%

The role of subchondral bone remodeling in osteoarthritis: Reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model

Hayami

Pickarski

Wesolowski

et al. 2004

Arthritis & Rheumatism

510

466

View full text Add to dashboard Cite

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“…TGF-beta also has welldocumented roles in chondrocyte maturation and endochondral ossification [14]. Autocrine and paracrine stimulation by TGF-b is important in the maintenance and expansion of the mesenchymal stem/progenitor cells, the progenitors of osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Elongated Styloid Process in Patients with Oral Submucous Fibrosis Using Panoramic Radiographs

Shivakumar

Batra

Upasi

et al. 2013

J. Maxillofac. Oral Surg.

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Introduction Oral submucous fibrosis (OSF) is an insidious disease affecting the oral cavity, pharynx, and upper digestive tract. It is characterized by a juxtaepithelial inflammatory reaction followed by fibroelastic change in the lamina propria and associated epithelial atrophy. Higher levels of TGF-b present in patients with OSF could be responsible for impetus to remnants of Reichert's cartilage present in styloid complex leading to partial or complete ossification of associated ligaments. So, a study was conducted to evaluate the elongation of the styloid process in patients with OSF by using panoramic radiographs. Materials and Methods Panoramic radiographs of patients with OSF were studied from 2007-2011. The apparent lengths of styloid process were measured with the help of divider and steel metric ruler. The length of the styloid process and/or ossification of stylomandibular ligaments which were longer than 30 mm were considered. Results Out of 47 patients, 35 patients (34 males & 1 female) met the inclusion criteria. Eleven patients (31.4%) were found to have elongated styloid processes which included 10 male patients and 1 female patient. Conclusion It had been estimated that between 2 % and 4% of the general population presents radiographic evidence of an ossified portion of the styloid complex. The high incidence of elongation of styloid process (31.4 %) in patients with oral submucous fibrosis highlights that progressive OSF might have some influence on elongation of styloid process.

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“…TGF-PI is a potential chemotactic stimulator for bone cells and promotes biosynthesis of extracellular matrix [30]. This growth factor actively regulated chondrogenesis and osteogenesis in bone regeneration [6,9,45]. The results of RT-PCR and immuno-histochemistry demonstrated that TGF-PI expression was elevated after ESW treatment.…”

Section: Discussionmentioning

confidence: 99%

Recruitment of mesenchymal stem cells and expression of TGF‐β1 and VEGF in the early stage of shock wave‐promoted bone regeneration of segmental defect in rats

Chen

Wurtz

Wang

et al. 2004

Journal Orthopaedic Research

170

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Extracorporeal shock wave (ESW) treatment has recently been established as a method to enhance bone repair. Here, we reported that ESW-promoted healing of segmental defect via stimulation of mesenchymal stem cell recruitment and differentiation into bone forming cells. Rats with a segmental femoral defect were exposed to a single ESW treatment (0.16 mJ/mm?, 1 Hz, 500 impulses). Cell morphology and histological changes in the defect region were assessed 3, 7, 14, and 28 days post-treatment. Presence of mesenchymal stem cell was assayed by immuno-staing for RPS9, a recently discovered marker, and also production of TGF-PI and VEGF was monitored. ESW treatment increased total cell density and the proportion of RP59 positive cells in the defect region. High numbers of round-and cuboidal-shaped cells strongly expressing RPS9 were initially found. Later, the predominant cell type was spindle-shaped fibroblastic cells, subsequently, aggregates of osteogenic and chondrogenic cells were observed. Histological observation suggested that bone marrow stem cells were progressively differentiated into osteoblasts and chondrocytes. RP59 staining was initially intense and decreased with the appearance of expression depended on the differentiation states of osteogenic and chondrogenic cells during the regeneration phase. Mature chondrocytes and osteoblasts exhibited only slight RP59 immunoreactivity. Expression of TGF-PI and VEGF-A mRNA in the defect tissues was also significantly increased ( P < 0.05) after ESW treatment as determined by RT-PCR. Intensive TGF-PI immuno-reactivity was induced immediately, whereas a lag period was observed for VEGF-A. Chondrocytes and osteoblasts at the junction of ossified cartilage clearly exhibited VEGF-A expression. Our findings suggest that recruitment of meseoblasts at the junction of ossified cartilage clearly exhibited mesenchymal stem cells is a critical step in bone reparation that is enhanced by ESW treatment. TGF-P1 and VEGF-A are proposed to play a chemotactic and mitogenic role in recruitment and differentiation of mesenchymal stem cells.

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Activation of Transforming Growth Factor β in Chondrocytes Undergoing Endochondral Ossification

Cited by 57 publications

References 60 publications

The role of subchondral bone remodeling in osteoarthritis: Reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model

The role of subchondral bone remodeling in osteoarthritis: Reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model

Evaluation of Elongated Styloid Process in Patients with Oral Submucous Fibrosis Using Panoramic Radiographs

Recruitment of mesenchymal stem cells and expression of TGF‐β1 and VEGF in the early stage of shock wave‐promoted bone regeneration of segmental defect in rats

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