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Background: Clinically oriented and easy to handle animal models are urgently needed to test pharmacologic treatment of cartilage trauma to reduce the resulting tissue damage by chondrocyte apoptosis and induction of matrix-degrading enzymes. Aim: To develop a biomechanically defined cartilage trauma model. Material and Methods: We constructed a novel trauma device that allows biomechanically defined force application to the load-bearing region of the medial and lateral femoral condyles in adult rabbits. The fixation to the femur was specially designed to avoid uncontrolled influx of blood into the joint. The device was tested on the articular femoral surface of cadaveric rabbits. Results: At a lower energy (1.0 J), the tests showed that superficial and partially deep fissuring, partial necrosis of the chondrocytes, and early proteoglycan loss occurred at the region of impact. Subchondral fractures could be excluded by micro CT. At higher energy (≥1.4 J), we observed more pronounced deep fissuring and in some cases complete shearing of the articular cartilage from the subchondral bone. Conclusion: Our model represents an easy to use method to create a biomechanically defined cartilage trauma and offers some advantages with respect to handling under aseptic surgical conditions and prevention of uncontrolled intra-articular bleeding from the bone marrow compartment for pharmacologic studies. [ABSTRACT FROM AUTHOR]

Dysplasia epiphysealis hemimelica (DEH) is a rare developmental disorder. The underlying pathophysiology is largely unclear. Its diagnosis is based on clinical findings and may be difficult due to its low incidence and close relationship to other disorders such as osteochondroma. We describe a 13-year-old boy who presented with a unilateral lesion of the left medial femoral condyle and left ankle. In addition to standard diagnostic tools such as radiographs and MRI, arthroscopy-guided biopsy was performed; histologic/immunohistochemical findings from cartilage-bone specimens confirmed the diagnosis and provided novel information toward a disease mechanism. The cellular phenotype of clustered chondrocytes exhibited characteristics of chondroprogenitor cells and terminally differentiated cells, suggesting dysregulation of resident progenitor cells. No other surgery was performed and during a 2 year period, we observed spontaneous ossification of the lesion associated with decreased joint impairment. Immunohistochemical analysis of the lesion provided a more accurate diagnosis and may contribute to unraveling potential novel mechanisms involved in its pathogenesis. [ABSTRACT FROM AUTHOR]

Background: CCN-proteins are known to be involved in development, homeostasis and repair of mesenchymal tissues. Since these processes implicate recruitment of cells with the potential to be committed to various phenotypes, we studied the effect of CYR61/CCN1 and WISP3/CCN6 on migration of human bone marrow derived mesenchymal stroma cells (MSCs) in comparison to in vitro osteogenic differentiated MSCs using a modified Boyden chamber assay. Results: CYR61 and WISP3 were purified as fusion proteins with a C-terminal Fc-tag from baculovirus infected SF21 cells using protein G sepharose columns. CYR61 and WISP3 stimulated cell migration of undifferentiated MSCs in a dose-dependent manner. CYR61 and WISP3 had similar effects on committed osteogenic precursor cells. Checkerboard analysis revealed that CYR61 and WISP3 stimulated true directed cell migration (chemotaxis) of MSCs and committed osteogenic precursors. In MSCs the chemotactic activity of WISP3 but not CYR61 was mediated through integrin α΍7#x03B2;5. Conclusion: Our results indicate that CYR61 and WISP3 can function as soluble ligands transmitting chemotactic signals to human MSCs but differ in the involvement of integrin α΍7#x03B2;5. This may be relevant for their possible role in connective tissue repair. [ABSTRACT FROM AUTHOR]

Spondyloepiphyseal dysplasia tarda (SEDT) is a genetically heterogeneous disorder often associated with the early onset of osteoarthrosis. The X-linked recessive form (SEDL) affects men and is characterized by reduced height, arm span exceeding total height, and barrel chest deformity. The radiographic phenotype comprises a hump-shaped deformity of vertebral bodies and mild epiphyseal dysplasia of the femoral head associated with early signs of hip arthrosis. The disorder is caused by mutations in the SEDL (or sedlin) gene on Xp22.12-p22.31. In 4 male patients from a German family, we identified a new nonsense mutation in SEDL exon 4 (C74A). The carrier status for the mutation could be confirmed in 2 women of the family, both of whom show no obvious signs of bone and joint diseases. SEDT should be kept in mind as a differential diagnosis in men with early "primary" bilateral osteoarthrosis [ABSTRACT FROM AUTHOR]

Cellular senescence is associated with various age‐related disorders and is assumed to play a major role in the pathogenesis of osteoarthritis (OA). Based on this, we tested a senolytic combination therapy using Dasatinib (D) and Quercetin (Q) on aged isolated human articular chondrocytes (hACs), as well as in OA‐affected cartilage tissue (OARSI grade 1–2). Stimulation with D + Q selectively eliminated senescent cells in both, cartilage explants and isolated hAC. Furthermore, the therapy significantly promoted chondroanabolism, as demonstrated by increased gene expression levels of COL2A1, ACAN, and SOX9, as well as elevated collagen type II and glycosaminoglycan biosynthesis. Additionally, D + Q treatment significantly reduced the release of SASP factors (IL6, CXCL1). RNA sequencing analysis revealed an upregulation of the anabolic factors, inter alia, FGF18, IGF1, and TGFB2, as well as inhibitory effects on cytokines and the YAP‐1 signaling pathway, explaining the underlying mechanism of the chondroanabolic promotion upon senolytic treatment. Accordingly, stimulation of untreated hAC with conditioned medium of D + Q‐treated cells similarly induced the expression of chondrogenic markers. Detailed analyses demonstrated that chondroanabolic effects could be mainly attributed to Dasatinib, while monotherapeutical application of Quercetin or Navitoclax did not promote the chondroanabolism. Overall, D + Q therapy restored the chondrogenic phenotype in OA hAC most likely by creating a pro‐chondroanabolic environment through the reduction of SASP factors and upregulation of growth factors. This senolytic approach could therefore be a promising candidate for further testing as a disease‐modifying osteoarthritis drug. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a progressive joint disease characterized by a continuous degradation of the cartilage extracellular matrix (ECM). The expression of the extracellular glycoprotein thrombospondin-4 (TSP-4) is known to be increased in injured tissues and involved in matrix remodeling, but its role in articular cartilage and, in particular, in OA remains elusive. In the present study, we analyzed the expression and localization of TSP-4 in healthy and OA knee cartilage by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and immunoblot. We found that TSP-4 protein expression is increased in OA and that expression levels correlate with OA severity. TSP-4 was not regulated at the transcriptional level but we detected changes in the anchorage of TSP-4 in the altered ECM using sequential protein extraction. We were also able to detect pentameric and fragmented TSP-4 in the serum of both healthy controls and OA patients. Here, the total protein amount was not significantly different but we identified specific degradation products that were more abundant in sera of OA patients. Future studies will reveal if these fragments have the potential to serve as OA-specific biomarkers. [ABSTRACT FROM AUTHOR]

To describe the 5 years' trajectories in functionality and pain of patients with hip or knee osteoarthritis and arthroplasty and analyze the association of these with long-term patients survival. Patients with OA receiving total hip or knee arthroplasty were recruited and completed two sets of standardized questionnaires for functionality and pain 6, 12, and 60 months postoperatively. Multivariate mixed models were conducted to assess trajectories over time and the resulting improvement per month during the last time period was included in a landmark-model to estimate adjusted hazard ratios for mortality. In total 809 patients with joint replacement were included (mean age 65.0 years, 62.2% female), 407 patients died (median follow-up 18.4 years). Both instruments of functionality and pain showed extensive improvement during the first 6 months. Baseline and change in functionality (both p < 0.001) and pain (p = 0.02) during the first 6 months were associated with mortality. Better values in functionality corresponded with improved survival whereas the association with the pain scores was inverse. In patients with hip and knee OA, an explicit improvement in function is seen within the first 6 months after arthroplasty. In addition, especially the functionality scores at baseline as well as their improvement showed an association with long-term patient survival. [ABSTRACT FROM AUTHOR]

Previous studies indicate an implication of the terminal complement complex (TCC) in disc degeneration (DD). To investigate the functional role of TCC in trauma-induced DD in vivo, the model of endplate (EP) drilling was first applied in rabbits using a C6-deficient rabbit strain in which no TCC formation was possible. In parallel the model of needle puncture was investigated. Using a minimally invasive surgical intervention, lumbar rabbit intervertebral discs (IVDs) were treated with EP drilling or needle puncture. Degenerative effects of both surgical interventions were assessed by Pfirrmann grading and T2 quantification of the IVDs based on high-resolution MRI (11.7 T), as well as radiographic determination of disc height index. Pfirrmann grading indicated significant degenerative effects after EP drilling. Contrary to our assumption, no evidence was found that the absence of TCC formation in C6-deficient rabbits reduces the development of DD compared to C6-sufficient animals. EP drilling was proven to be suitable for application in rabbits. However, results of the present study do not provide clear evidence of a central functional role of TCC within DD and suggest that TCC deposition in DD patients may be primarily considered as a marker of complement activation during DD progression.

Accumulation of dysfunctional chondrocytes has detrimental consequences on the cartilagehomeostasis and is thus thought to play a crucial role during the pathogenesis of osteoarthritis(OA). However, the underlying mechanisms of phenotypical alteration in chondrocytes areincompletely understood. Here, we provide evidence that disruption of the intracellularvimentin network and consequent phenotypical alteration in human chondrocytes results in anexternalization of the intermediate filament. The presence of the so-called cell surfacevimentin (CSV) on chondrocytes was associated with the severity of tissue degeneration inclinical OA samples and was enhanced after mechanical injury of cartilage tissue. By meansof a doxorubicine-based in vitro model of stress-induced premature senescence (SIPS), wecould confirm the connection between cellular senescence and amount of CSV. AlthoughsiRNA-mediated silencing of CDKN2A clearly reduced the senescent phenotype as well asCSV levels of human chondrocytes, cellular senescence could not be completely reversed.Interestingly, knockdown of vimentin resulted in a SIPS-like phenotype and consequentlyincreased CSV. Therefore, we concluded that the integrity of the intracellular vimentinnetwork is crucial to maintain cellular function in chondrocytes. This assumption could beconfirmed by chemically- induced collapse of the vimentin network, which resulted in cellularstress and enhanced CSV expression. Regarding its biological function, CSV was found to beassociated with enhanced chondrocyte adhesion and plasticity. While osteogenic capacitiesseemed to be enhanced in chondrocytes expressing high levels of CSV, the chondrogenicpotential was clearly compromised. Overall, our study reinforces the importance of thevimentin network in maintenance of the chondrogenic phenotype and introduces CSV as anovel membrane-bound marker of dysfunctional chondrocytes., Competing Interests: JR, RB No competing interests declared, (© 2023, Riegger and Brenner.)

Terminal complement complex (TCC) deposition was identified in human degenerated discs. To clarify the role of terminal complement activation in disc degeneration (DD), we investigated respective activating mechanisms and cellular effects in annulus fibrosus (AF) cells. Isolated cells from human AF, nucleus pulposus (NP), and endplate (EP) were stimulated with human serum alone or with zymosan and treated with either the C3 inhibitor Cp40 or the C5 antibody eculizumab. Complement activation was determined via anaphylatoxin generation and TCC deposition detection. Thereby, induced catabolic effects were evaluated in cultured AF cells. Moreover, C5 cleavage under degenerative conditions in the presence of AF cells was assessed. Zymosan-induced anaphylatoxin generation and TCC deposition was significantly suppressed by both complement inhibitors. Zymosan induced gene expression of ADAMTS4, MMP1, and COX2. Whereas the C3 blockade attenuated the expression of ADAMTS4, the C5 blockade reduced the expression of ADAMTS4, MMP1, and COX2. Direct C5 cleavage was significantly enhanced by EP conditioned medium from DD patients and CTSD. These results indicate that terminal complement activation might be functionally involved in the progression of DD. Moreover, we found evidence that soluble factors secreted by degenerated EP tissue can mediate direct C5 cleavage, thereby contributing to complement activation in degenerated discs.

20 years ago, we described a human cell strain derived from subcutaneous adipose tissue of an infant supposed to have Simpson-Golabi-Behmel Syndrome (SGBS), thus called "SGBS cells". Since then, these cells have emerged as the most commonly used cell model for human adipogenesis and human adipocyte biology. Although these adipocyte derived stem cells have not been genetically manipulated for transformation or immortalization, SGBS cells retain their capacity to proliferate and to differentiate into adipocytes for more than 50 population doublings, providing an almost unlimited source of human adipocyte progenitor cells. Original data obtained with SGBS cells led to more than 200 peer reviewed publications comprising investigations on adipogenesis and browning, insulin sensitivity, inflammatory response, adipokine production, as well as co-culture models and cell-cell communication. In this article, we provide an update on the characterization of SGBS cells, present basic methods for their application and summarize results of a systematic literature search on original data obtained with this cell strain., (© 2022. The Author(s).)

Purpose: Formation of terminal complement complex (TCC), a downstream complement system activation product inducing inflammatory processes and cell lysis, has been identified in degenerated discs. However, it remains unclear which molecular factors regulate complement activation during disc degeneration (DD). This study investigated a possible involvement of the pro-inflammatory cytokine interleukin-1β (IL-1β) and the lysosomal protease cathepsin D (CTSD)., Methods: Disc biopsies were collected from patients suffering from DD (n = 43) and adolescent idiopathic scoliosis (AIS, n = 13). Standardized tissue punches and isolated cells from nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) were stimulated with 5% human serum (HS) alone or in combination with IL-1β, CTSD or zymosan. TCC formation and modulation by the complement regulatory proteins CD46, CD55 and CD59 were analysed., Results: In DD tissue cultures, IL-1β stimulation decreased the percentage of TCC + cells in AF and EP (P < 0.05), whereas CTSD stimulation significantly increased TCC deposition in NP (P < 0.01) and zymosan in EP (P < 0.05). Overall, the expression of CD46, CD55 and CD59 significantly increased in all isolated cells during culture (P < 0.05). Moreover, cellular TCC deposition was HS concentration dependent but unaffected by IL-1β, CTSD or zymosan., Conclusion: These results suggest a functional relevance of IL-1β and CTSD in modulating TCC formation in DD, with differences between tissue regions. Although strong TCC deposition may represent a degeneration-associated event, IL-1β may inhibit it. In contrast, TCC formation was shown to be triggered by CTSD, indicating a multifunctional involvement in disc pathophysiology., (© 2021. The Author(s).)

Purpose: The complement system is a crucial part of innate immunity. Recent work demonstrated an unexpected contribution to tissue homeostasis and degeneration. This study investigated for the first time, in human disc tissues, the deposition profile of the complement activation product terminal complement complex (TCC), an inflammatory trigger and inducer of cell lysis, and its inhibitor CD59, and their correlation with the degree of disc degeneration (DD)., Methods: Disc biopsies were collected from patients diagnosed with DD (n = 39, age 63 ± 12) and adolescent idiopathic scoliosis (AIS, n = 10, age 17 ± 4) and compared with discs from healthy Young (n = 11, age 7 ± 7) and Elder (n = 10, age 65 ± 15) donors. Immunohistochemical detection of TCC and CD59 in nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) was correlated with age, Pfirrmann grade and Modic changes., Results: Higher percentage of TCC+ cells was detected in the NP and EP of DD compared to Elder (P < 0.05), and in the EP of Young versus Elder (P < 0.001). In DD, TCC deposition was positively correlated with Pfirrmann grade, but not with Modic changes, whereas for Young donors, a negative correlation was found with age, indicating TCC's involvement not only in DD, but also in early stages of skeletal development. Higher CD59 positivity was found in AIS and DD groups compared to Young (P < 0.05), and it was negatively correlated with the age of the patients., Conclusion: TCC deposition positively correlated with the degree of disc degeneration. A functional relevance of TCC may exist in DD, representing a potential target for new therapeutics.

Joint injuries are highly associated with cell death and development of posttraumatic osteoarthritis (PTOA). The present study focused on necroptosis as a possible modality of chondrocyte death after cartilage trauma and its relevance in OA disease in general. For this purpose, apoptosis- and necroptosis-associated markers were determined in highly degenerated (ICRS ≥ 3) as well as macroscopically intact cartilage tissue (ICRS ≤ 1) by means of real-time PCR and immunohistochemistry (IHC). Moreover, influence of blunt trauma and/or stimulation with cycloheximide (CHX), TNF-a, and caspase-inhibitor zVAD were investigated in cartilage explants (ICRS ≤ 1). Further characterization of necroptosis was performed in isolated chondrocytes. We found that gene expression levels of RIPK3 (4.2-fold, P < 0.0001) and MLKL (2.7-fold, P < 0.0001) were elevated in highly degenerated cartilage tissue, which was confirmed by IHC staining. After ex vivo trauma and/or CHX/TNF stimulation, addition of zVAD further enhanced expression of necroptosis-related markers as well as release of PGE2 and nitric oxide, which was in line with increased cell death and subsequent release of intracellular HMGB1 and dsDNA in CHX/TNF stimulated chondrocytes. However, trauma and/or chemically induced cell death and subsequent release of pro-inflammatory mediators could be largely attenuated by RIPK1-inhibitor necrostatin 1 or antioxidant N-acetylcysteine. Overall, the study provided clear evidence of necroptotic cell death in OA disease. Moreover, a possible link between cartilage injury and necroptotic processes was found, depending on oxidative stress and cytokine release. These results contribute to further understanding of cell death in PTOA and development of novel therapeutic approaches.

The terminal complement complex (TCC) is formed on activation of the complement system, a crucial arm of innate immunity. TCC formation on cell membranes results in a transmembrane pore leading to cell lysis. In addition, sublytic TCC concentrations can modulate various cellular functions. TCC-induced effects may play a role in the pathomechanisms of inflammatory disorders of the bone, including rheumatoid arthritis and osteoarthritis. In this study, we investigated the effect of the TCC on bone turnover and repair. Mice deficient for complement component 6 (C6), an essential component for TCC assembly, and mice with a knockout of CD59, which is a negative regulator of TCC formation, were used in this study. The bone phenotype was analyzed in vivo, and bone cell behavior was analyzed ex vivo. In addition, the mice were subjected to a femur osteotomy. Under homeostatic conditions, C6-deficient mice displayed a reduced bone mass, mainly because of increased osteoclast activity. After femur fracture, the inflammatory response was altered and bone formation was disturbed, which negatively affected the healing outcome. By contrast, CD59-knockout mice only displayed minor skeletal alterations and uneventful bone healing, although the early inflammatory reaction to femur fracture was marginally enhanced. These results demonstrate that TCC-mediated effects regulate bone turnover and promote an adequate response to fracture, contributing to an uneventful healing outcome., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Activation of both the complement and coagulation cascade after trauma and subsequent local and systemic inflammatory response represent a major scientific and clinical problem. After severe tissue injury and bone fracture, exposure of innate immunity to damaged cells and molecular debris is considered a main trigger of the posttraumatic danger response. However, the effects of cellular fragments (e.g., histones) on complement activation remain enigmatic. Furthermore, direct effects of "broken" bone and cartilage surfaces on the fluid phase response of complement and its interaction with key cells of connective tissues are still unknown. Here, we summarize data suggesting direct and indirect complement activation by extracellular and cellular danger associated molecular patterns. In addition, key complement components and the corresponding receptors (such as C3aR, C5aR) have been detected on "exposed surfaces" of the damaged regions. On a cellular level, multiple effects of complement activation products on osteoblasts, osteoclasts, chondrocytes and mesenchymal stem cells have been found.In conclusion, the complement system may be activated by trauma-altered surfaces and is crucially involved in connective tissue healing and posttraumatic systemic inflammatory response.

Injury to articular cartilage is often associated with an inflammatory reaction and frequently results in the development of post-traumatic osteoarthritis (post-traumatic OA). Cell death, inflammation and loss of proteoglycans participate in these mechanisms with p38MAPK being one of the pivotal signaling kinases. Therefore, the interaction of trauma and of the pro-inflammatory cytokine IL-1β was investigated in an in vitro tissue model of human osteoarthritic cartilage. Trauma was induced by impacting cartilage explants with a drop-tower system and its effect was measured in terms of cell survival, gene expression and the release of mediators. In addition, the effect of concomitant IL‑1β stimulation and p38MAPK inhibition by SB203580 was investigated. We found a significant decrease in chondrocyte viability after trauma, but no additional effect of IL-1β stimulation. SB203580 had a tendency to improve cell survival suggesting a role for p38 signaling in cell viability after impact in an inflammatory environment. We showed that various mediators are released in response to trauma with or without IL-1β stimulation, differing in composition and time response. Trauma resulted in an increased release of IL-6, whereas TNF-α and IL-1β release was unaffected. Prostaglandin (PG) and NO synthesis pathways were both affected by trauma and/or IL-1β. We demonstrate for the first time an elevated release of prostaglandin D2 (PGD2) by human articular cartilage in response to a single mechanical impact. The up-regulation of mediators was time-dependent, with a more early increase of PGD2 compared to prostaglandin E2 (PGE2) and a late induction of NO by co-stimulation with IL-1β between 6 and 24 h.

We have previously reported that star shaped poly(ethylene oxide-stat-propylene oxide) macromers with 80% EO content and isocyanate functional groups at the distal ends [NCO-sP(EO-stat-PO)] can be used to generate coatings that are non-adhesive but easily functionalized for specific cell adhesion. In the present study, we investigated whether the NCO-sP(EO-stat-PO) surfaces maintain peptide configuration-specific cell-surface interactions or if differences between dissimilar binding molecules are concealed by the coating. To this end, we have covalently immobilized both linear-RGD peptides (gRGDsc) and cyclic-RGD (RGDfK) peptides in such coatings. Subsequently, SaOS-2 or human multipotent mesenchymal stromal cells (MSC) were seeded on these substrates. Cell adhesion, spreading and survival was observed for up to 30 days. The time span for cell adherence was not different on linear and cyclic RGD peptides, but was shorter in comparison to the unmodified glass surface. MSC proliferation on cyclic RGDfK modified coatings was 4 times higher than on films functionalized by linear gRGDsc sequences, underlining that the NCO-sP(EO-stat-PO) film preserves the configuration-specific biochemical peptide properties. Under basal conditions, MSC expressed osteogenic marker genes after 14 days on cyclic RGD peptides, but not on linear RGD peptides or the unmodified glass surfaces. Our results indicate specific effects of these adhesion peptides on MSC biology and show that this coating system is useful for selective testing of cellular interactions with adhesive ligands.

Articular chondrocytes respond to extracellular influences by activating signaling pathways which change gene expression. One key signal transduction pathway of inflammatory joint disease is mediated by the p38MAPK which is known to be activated by the pro-inflammatory cytokine IL-1beta. We used the p38MAPK inhibitor SB203580 and a whole human genome microarray in an in vitro inflammation model to identify genes regulated by this pathway in human chondrocytes. We found that 1,141 genes were regulated by IL-1beta, and 646 genes were regulated by the inhibitor whereas 116 genes were co-regulated by both substances. To elucidate the overall effect of SB203580, a GoMiner pathway analysis was performed which revealed involvement of versatile biological processes. Predominantly affected terms were 'response to stimulus', 'oxygen metabolism' and 'ligase activity'. We discuss herein the relevance and function of affected fields including the involved genes and unexpected effects of p38MAPK inhibition as it relates to the context of cartilage. Our results do not predict a pro-apoptotic or cancer promoting effect and markedly extend the knowledge on p38MAPK inhibition in chondrocytes beyond primary target genes.

The aim of the study was to investigate the biocompatibility, degradation, and biomechanical properties of beta-TCP (Cerasorb) in a weight-bearing sheep model. beta-TCP implant prototypes were implanted in the tibial head of adult merino sheep. After 6 and 12 months material explants were harvested for biomechanical, histological, and histomorphometrical analysis. Corresponding bone specimens of the intact bone of the contralateral leg were used as controls in the biomechanical test. Compression tests showed higher values for maximum fracture load, yield strength, and compression modulus after 6 and 12 months compared to control. Microscopically, the implants showed good osteoconduction and were incorporated into the bone; however, relevant amounts of beta-TCP were still present after 12 months. Histomorphological results revealed that beta-TCP had partially degraded between implantation and 6 months, but its share remained constant between 6 and 12 months. The bone volume fraction in the area of the implant (46% +/- 6.5%) was initially higher than in the corresponding bone area of the contralateral leg (31% +/- 9.6%), but after 12 months declined to 29% +/- 9.4% (control: 33% +/- 8.3%), while the share of beta-TCP remained constant at 36% +/- 12.2%. These findings were supported by microradiographic data. In conclusion, in a weight bearing implantation model beta-TCP showed good biocompatibility, osseointegration and beginning degradation, even though it was not further degraded between 6 and 12 months., (Copyright 2004 Wiley Periodicals, Inc.)