Chondrogenic differentiation of bovine synovium: Bone morphogenetic proteins 2 and 7 and transforming growth factor β1 induce the formation of different types of cartilaginous tissue

Shintani, Nahoko; Hunziker, Ernst B.

doi:10.1002/art.22701

Cited by 101 publications

(90 citation statements)

References 46 publications

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“…This suggests that either proliferation was not a prerequisite for chondrogenic differentiation or that IdU-labeled cells had divided very few times before CIdU was administered 8 days after surgery, so that they retained IdU beyond the period of proliferation but were negative for CIdU. Although we cannot exclude the possibility that IdU-positive chondrocytes migrated out of the articular cartilage into the synovium, our study indicated an obvious contribution of synovial cells to the process of cartilage metaplasia in synovium, in keeping with previous observations that treatment of synovial tissue explants in vitro with chondrogenic growth factors induced cartilage formation (40,41). Cartilage metaplasia was observed throughout the knee joint synovium but was much more pronounced at the transition zone where the synovium connects to the articular cartilage, mimicking the chondrophytes observed in osteoarthritis.…”

Section: Discussionsupporting

confidence: 89%

Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo

Kurth¹,

Dell’Accio²,

Crouch³

et al. 2011

Arthritis & Rheumatism

178

174

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Objective. We previously reported that human synovium contains cells that, after culture expansion, display properties of mesenchymal stem cells (MSCs). The objective of this study was to identify MSCs in native synovium in vivo.Methods. To identify stem cells in the synovium in vivo, a double nucleoside analog cell-labeling scheme was used in a mouse model of joint-surface injury. For labeling of slow-cycling cells, mice received iododeoxyuridine (IdU) for 30 days, followed by a 40-day washout period. For labeling of cells that proliferate after injury, mice underwent knee surgery to produce an articular cartilage defect and received chlorodeoxyuridine (CIdU) for 4 days, starting at multiple time points after surgery. Unoperated and sham-operated joints served as controls. Knee joint paraffin sections were analyzed by double and triple immunostaining to detect nucleoside analogs, conventional MSC markers, and chondrocytelineage markers.Results. Long-term-retaining, slow-cycling IdUpositive cells were detected in the synovium. At 4 days and 8 days after injury, there was marked proliferation of IdU-positive cells, which costained for CIdU. IdUpositive cells were nonhematopoietic, nonendothelial stromal cells, were distinct from pericytes, and stained positive for MSC markers. MSCs were phenotypically heterogeneous and located in topographically distinct niches in the lining layer and the subsynovial tissue. Twelve days after injury, double nucleoside-labeled cells within synovium were embedded in cartilagespecific metachromatic extracellular matrix and costained positive for the chondrocyte-lineage markers Sox9 and type II collagen.Conclusion. Our findings provide the first evidence of the existence of resident MSCs in the knee joint synovium that undergo proliferation and chondrogenic differentiation following injury in vivo.

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Section: Discussionsupporting

confidence: 89%

Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo

Kurth¹,

Dell’Accio²,

Crouch³

et al. 2011

Arthritis & Rheumatism

178

174

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“…This indicates that BMP-7 interfered with caspase-mediated cell death after mechanical injury, and could play a role in inhibition of cell-cell signaling leading to apoptosis. Because there was no clear evidence of additional cells 43 participating in the repair process, our data suggest that BMP-7 allowed survival and retention of native chondrocytes that replenished and remodeled the damaged matrix. Measuring cell viability and metabolic activity per unit volume of cartilage would be a more reliable evidence of this hypothesis, but this would be technically demanding and require a larger experiment.…”

mentioning

confidence: 75%

BMP‐7 protects against progression of cartilage degeneration after impact injury

Hurtig

Chubinskaya

Dickey

et al. 2008

Journal Orthopaedic Research

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In vivo studies were used to characterize a model of cartilage injury leading to osteoarthritis progression in the medial femorotibial joint of sheep. In three subsequent studies, bilateral impact injuries were created and one joint received intraarticular injections of 340 mg of rhBMP-7 protein in a collagen particle carrier while the contralateral knee received the vehicle alone. Sheep were allocated to three groups that received intraarticular injections on day 0 (group A), 21 (group B), or 90 (group C) after experimental knee injury. In each group the, joints were evaluated for signs of osteoarthritis progression 90 days after the last treatment using India ink stained area, OARSI histological scoring, cartilage sGAG content, immunostaining for apoptosis (TUNEL), caspase-3, collagen degradation (Col 2 3/4C short collagen epitope), and the endogenous (pro-) form of BMP-7 protein. Knee joints that received rhBMP-7 immediately after injury had small focal lesions at the injury site that did not progress into the surrounding cartilage. Joints that received BMP-7 3 weeks after injury were improved and had limited progression compared to controls, but joints that received the protein 12 weeks after injury had no statistically significant improvement. These studies suggest that BMP-7 may be chondroprotective after traumatic injury in patients if it is administered within 3 to 4 weeks of the index injury. The mechanism of protection after sublethal injury appeared to be an increased survival of chondrocytes that are able to participate in the repair process. ß

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“…43 Synovial explants treated with BMP-2 expressed the cartilage-specific markers type II collagen and proteoglycan, but by 6 weeks in culture, the authors noted the grossly hypertrophic state of the differentiated synovial cells. 44 In a more recent experiment, ATDC5 cells, a chondrogenic cell line from the AT805 mouse teratocarcinoma, were shown to have enhanced proteoglycan synthesis up to 4 weeks in cultures in which BMP-2 was stably over-expressed, but the same study found that alkaline phosphatase expression and activity also increased in response to BMP-2 in as little as 9 days. 45 Similarly, BMP-2 promoted hypertrophy of primary chondrocytes grown for 4 weeks on substrates that support three-dimensional cell morphology.…”

Section: Discussionmentioning

confidence: 98%

Influence of Bone Morphogenetic Protein-2 on the Extracellular Matrix, Material Properties, and Gene Expression of Long-Term Articular Chondrocyte Cultures: Loss of Chondrocyte Stability

Krawczak

Carlson²,

Lewis

2009

Tissue Engineering Part A

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The aim of this study was to determine the effects of bone morphogenetic protein-2 (BMP-2) on articular chondrocyte tissues grown as monolayers in vitro for up to 8 weeks. Articular chondrocytes were isolated from New Zealand White rabbits and plated in monolayer cultures. The cultures were supplemented with 100 ng=mL of BMP-2 for up to 8 weeks and the extracellular matrix (ECM) composition, material properties, and messenger RNA (mRNA) expression were analyzed. mRNA expression of cartilage-specific genes, type II collagen, and aggrecan showed that BMP-2 enhanced chondrocyte stability for up to 3 weeks. After 3 weeks in culture, there was substantially more type I collagen expression and more osteopontin and runt-related transcription factor 2 expression in 5-and 8-week cultures treated with BMP-2 than in controls. Additionally, matrix metalloproteinase-13 and ADAMTS-5 (A disintegrin-like and metalloproteinase with thrombospondin 5) were upregulated in 5-and 8-week cultures treated with BMP-2, coinciding with a loss of ECM density, collagen, and proteoglycan. Eight-week tissue stimulated with BMP-2 was more fragile and tore more easily when removed from the culture dish as compared to controls, suggesting temporal limitations to the effectiveness of BMP-2 in monolayer systems and perhaps other models to enhance the generation of a cartilage-like tissue for tissue engineering purposes.

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Chondrogenic differentiation of bovine synovium: Bone morphogenetic proteins 2 and 7 and transforming growth factor β1 induce the formation of different types of cartilaginous tissue

Cited by 101 publications

References 46 publications

Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo

Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo

BMP‐7 protects against progression of cartilage degeneration after impact injury

Influence of Bone Morphogenetic Protein-2 on the Extracellular Matrix, Material Properties, and Gene Expression of Long-Term Articular Chondrocyte Cultures: Loss of Chondrocyte Stability

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