Enhancement of Periosteal Chondrogenesis In Vitro Dose-Response for Transforming Growth Factor-Beta 1 (TGF-??1)

Miura, Yasushi; Fitzsimmons, James S.; Commisso, Cinzia N.; Gallay, Stephen H.; O’Driscoll, Shawn W.

doi:10.1097/00003086-199404000-00043

Cited by 85 publications

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“…Periosteum transplanted into a joint has the potential to repair articular defects with hyaline-like cartilage [32,37,38,42,. This same chondrogenic potential can be demonstrated in vitro [15,30,35,36,42,56,57]. However, the standard organ culture model to date involving whole explants of periosteum has required the addition of fetal bovine serum to the media.…”

Section: Introductionmentioning

confidence: 98%

“…Experimental models involving cell or tissue culture of chondrocytes or chondrogenic cells have demonstrated the feasibility of growing cartilage in vitro. These include, but are not limited to, the use of chondrocytes [3,16,17], mesenchymal stem cells [ 18, 19,67] and whole tissues such as periosteum [ 15,30,35,36,42,56,57] or perichondrium [1, 2,5,7,[9][10][11][12]21,46,47,50,58,59,65] genesis. Many of these systems have relied on the use of fetal bovine serum in the medium.…”

Section: Introductionmentioning

confidence: 99%

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Serum‐free media for periosteal chondrogenesis in vitro

Fitzsimmons

Sanyal

Gonzalez

et al. 2004

Journal Orthopaedic Research

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Organ culture studies involving whole explants of periosteum have been useful for studying chondrogenesis, but to date the standard culture model for these explants has required the addition of fetal bovine serum to the media. Numerous investigators have succeeded in culturing chondrocytes and embryonic cells in serum-free conditions but there have been no studies focused on achieving a defined, serum-free media for culturing periosteal explants. The purpose of the present investigation was to determine if whole periosteal explants can be grown and produce cartilage in serum-free conditions, and to define the minimum media supplements that would be conducive to chondrogenesis. 321 periosteal explants were obtained from the medial proximal tibiae of 31 two month-old NZ white rabbits and cultured using a published agarose suspension organ culture model and DMEM for six weeks. The explants were cultured with and without fetal bovine serum or bovine serum albumin and exposed to transforming growth factor beta alone, a combination of growth factors we call ChondroMix (10 ng/ml transforming growth factor beta, 50 ng/ml basic fibroblast growth factor, and 5 pg/ml growth hormone), and/or ITS+ (2.08 pg/ml each of insulin, transferrin, and selenious acid, plus 1.78 pg/ml linoleic acid and 0.42 mg/ml BSA). Maximal chondrogenic stimulation in this study was observed with the combination of ChondroMix and ITS+. However, the minimal requirement to match or exceed the level of chondrogenic stimulation seen in the standard model (TGF-1 in 100/0 FBS) was achieved simply by the addition of 2.0 pg/ml insulin in 0.10/0 BSA-containing medium (p < 0.05). Therefore, based on our results, it would be reasonable to assume that insulin is the component in ITS+ responsible for the observed increase in total cartilage growth. Lower concentrations of insulin were not effective, suggesting that the observed effect of insulin requires activation of the IGF-1 receptor.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Serum‐free media for periosteal chondrogenesis in vitro

Fitzsimmons

Sanyal

Gonzalez

et al. 2004

Journal Orthopaedic Research

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“…During periosteal neochondrogenesis in vivo and in vitro, cell morphology varies and appears to change over time [39,44,46]. Although little is known regarding the proliferative capacity or activity in developing periosteal neochondrocytes, we hypothesized that such activity should correlate with cell morphology.…”

Section: Introductionmentioning

confidence: 99%

Histomorphological and proliferative characterization of developing periosteal neochondrocytes in vitro

Ito

Sanyal

Fitzsimmons

et al. 2001

Journal Orthopaedic Research

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Periosteal chondrogenesis is relevant to cartilage repair and fracture healing. Cell proliferation is a limiting factor of cartilage production. We used an in vitro organ culture model to test the hypothesis that proliferative activity correlates with cell morphology. One hundred and four periosteal explants from 26 two-month old New Zealand rabbits were cultured for up to 42 days. They were analyzed histomorphologically, and immunohistochemically with proliferative cell nuclear antigen (PCNA). The periosteal neocartilage displayed a consistent zonal pattern of chondrocyte cell shapes. ThefIut cell zone from day 7 to 21, consisted of uniform-sized small spindle-shaped cells. The round cell zone, which appeared on day 14, consisted of variable-sized round cells averaging 510 i 250 pm2 in area. They were subdivided into small round ( 4 1 0 pm') and large round cells (>510 pm2). The proliferative index was highest in the small round cell group (32 I-t 6%), intermediate in the flat cell group (27 f 6'1/n), and lowest in the large round cell group (20 k 7%) ( P < 0.001 ). Furthermore, the proliferative indices in the round cell group were inversely proportional to cell size. Therefore, (1 ) there is a sequential progression of cell morphology during periosteal chondrogenesis, (2) cell differentiation is arrested prior to terminal differentiation for some cells and not for others, and (3) proliferative activity is strongly related to cell morphology. This organ culture model provides us with opportunities to study the regulation of terminal chondrocyte differentiation and the control of cell proliferation. This will contribute to our understanding of cartilage repair, fracture healing and growth plate physiology. 0 100 1

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“…However, this method has inherent limitations, among which is the prolonged recovery period required before the repair sites are able to tolerate normal joint stresses. To overcome this problem, current studies focus on stepping up tissue healing by (1) introducing cell scaffolds that provide the biomechanical strength needed to withstand early T Kamarul et al Surgically treated and untreated focal cartilage damage exposure to joint stresses, or by (2) enhancing tissue differentiation through growth factor-induced cellular expression (Miura et al, 1994;Brittberg, 1999;Brittberg et al, 2001;Brittberg, 2008). Although the role of stimulating factors and hormones to increase phenotypic cell expression has been well established in various in vitro models, their clinical applications have not been as forthcoming (Miura et al, 1994;Mercy Tissue Engineering, 2002;Brittberg, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…To overcome this problem, current studies focus on stepping up tissue healing by (1) introducing cell scaffolds that provide the biomechanical strength needed to withstand early T Kamarul et al Surgically treated and untreated focal cartilage damage exposure to joint stresses, or by (2) enhancing tissue differentiation through growth factor-induced cellular expression (Miura et al, 1994;Brittberg, 1999;Brittberg et al, 2001;Brittberg, 2008). Although the role of stimulating factors and hormones to increase phenotypic cell expression has been well established in various in vitro models, their clinical applications have not been as forthcoming (Miura et al, 1994;Mercy Tissue Engineering, 2002;Brittberg, 2008). Glucosamine sulphate (GS) and chondroitin sulphate (CS) are two most frequently prescribed nutritional supplements for the treatment of osteoarthritis (Noack et al, 1994;Matheson and Perry, 2003;Richy et al, 2003), yet controversy surrounds their efficacy and definitive mechanism of action.…”

Section: Introductionmentioning

confidence: 99%

A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage

Kamarul¹,

Ab‐Rahim²,

Tumin³

et al. 2011

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The effects of Glucosamine Sulphate (GS) and Chondroitin Sulphate (CS) on the healing of damaged and repaired articular cartilage were investigated. This study was conducted using 18 New Zealand white rabbits as experimental models. Focal cartilage defects, surgically created in the medial femoral condyle, were either treated by means of autologous chondrocyte implantation (ACI) or left untreated as controls. Rabbits were then divided into groups which received either GS+/-CS or no pharmacotherapy. Three rabbits from each group were sacrificed at 12 and 24 weeks post-surgery. Knees dissected from rabbits were then evaluated using gross quantification of repair tissue, glycosaminoglycan (GAG) assays, immunoassays and histological assessments. It was observed that, in contrast to untreated sites, surfaces of the ACI-repaired sites appeared smooth and continuous with the surrounding native cartilage. Histological examination demonstrated a typical hyaline cartilage structure; with proteoglycans, type II collagen and GAGs being highly expressed in repair areas. The improved regeneration of these repair sites was also noted to be significant over time (6 months vs. 3 months) and in GS and GS+CS groups compared to the untreated (without pharmacotherapy) group. Combination of ACI and pharmacotherapy (with glucosamine sulphate alone/ or with chondroitin sulphate) may prove beneficial for healing of damaged cartilage, particularly in relation to focal cartilage defects.

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Enhancement of Periosteal Chondrogenesis In Vitro Dose-Response for Transforming Growth Factor-Beta 1 (TGF-??1)

Cited by 85 publications

References 0 publications

Serum‐free media for periosteal chondrogenesis in vitro

Serum‐free media for periosteal chondrogenesis in vitro

Histomorphological and proliferative characterization of developing periosteal neochondrocytes in vitro

A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage

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