Pharmacological Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification Treatment.

Calcification of soft tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured tissues. But some of them become divergent to the direction of ossification in the local pathological microenvironment, thereby representing a cellular target for pharmacological approach. We observed that HIF-2alpha (encoded by EPAS1 inclined form) signaling is markedly activated within stem/progenitor cells recruited at calcified sites of diseased human tendons and heart valves. Proinflammatory microenvironment, rather than hypoxia, is correlated with HIF-2alpha activation and promoted osteochondrogenic differentiation of tendon stem/progenitor cells (TSPCs). Abnormal upregulation of HIF-2alpha served as a key switch to direct TSPCs differentiation into osteochondral-lineage rather than teno-lineage. Notably, Scleraxis (Scx), an essential tendon specific transcription factor, was suppressed on constitutive activation of HIF-2alpha and mediated the effect of HIF-2alpha on TSPCs fate decision. Moreover, pharmacological inhibition of HIF-2alpha with digoxin, which is a widely utilized drug, can efficiently inhibit calcification and enhance tenogenesis in vitro and in the Achilles's tendinopathy model. Taken together, these findings reveal the significant role of the tissue stem/progenitor cells fate decision and suggest that pharmacological regulation of HIF-2alpha function is a promising approach for soft tissue calcification treatment.

Pure alumina bearings with cementless stems versus sandwich bearings with cemented stems in total hip arthroplasty.

BACKGROUND: Ceramic bearing surfaces have been introduced to prevent osteolysis after total hip arthroplasty (THA), but little is known about the difference in clinical and radiological results between pure alumina and sandwich alumina bearings. The purpose of this study was to analyze the results obtained with third-generation alumina-on-alumina THA with two different designs both in liner and femoral stem fixation after a minimum follow-up of 4.2 years. METHODS: The results of 195 primary alumina-on-alumina THAs in 167 patients were evaluated. The procedures were performed between January 1998 and October 2006. Three patients died and 11 patients were lost to follow-up, leaving a total of 153 patients (181 hips) available for study. In the 88 group A patients, 107 hips were implanted using pure alumina bearings with cementless femoral stems. These patients were followed for (6.84 ± 1.49) years. In the 65 group B patients, 74 hips were implanted using sandwich alumina ceramic bearings with cemented femoral stems. These patients had a follow-up period of (7.73 ± 1.60) years. Patients in both groups were evaluated clinically and radiographically. RESULTS: One ceramic liner fracture occurred in group A and five took place in group B (P < 0.05), four of them revised for liner fracture. In each group, one acetabular shell migration happened without liner breakage and two hips developed deep infections, and all these six hips received revisions. Nine femoral components loosened in group B, with seven undergoing revisions. Kaplan-Meier survivorship at 5 years for revision of any component for any reason in group A was 96.26% compared to 90.54% in group B (P < 0.05). Better function was determined in group A (average Harris hip scores: 92.13 ± 2.85) than in group B (average Harris hip scores: 86.03 ± 4.21) and the difference was significant (P < 0.05). Squeaking was not recorded in either group. CONCLUSIONS: The sandwich design of the acetabular bearings can not reduce the migration rate in ceramic bearings but increase the liner fracture rate compared to pure ceramic liners. The high loosening rate in fluted and taped designed cemented stems with sandwich liners warrant caution to their use.

[Intermediate outcomes of alumina-on-alumina bearing total hip arthroplasty].

OBJECTIVE: To explore the intermediate outcomes of third-generation alumina-on-alumina total hip arthroplasty (THA). METHODS: A consecutive series of 165 primary alumina-on-alumina total hip arthroplasties were performed in 135 patients. Three patients died and 13 patients lost follow-up so that a total of 119 patients (146 hips) were available for study. The mean patient age was 53.4 ± 11.0 years old (range: 26 - 79). Hydroxyapatite. (HA)-coated press-fit acetabular cups were used in all cases. At femoral side, 123 cases were implanted with HA-coated uncemented stems and 23 cases implanted with high polished double taped cemented stems. All patients were evaluated clinically and radiographically after a minimal follow-up duration of 60 months. RESULTS: The preoperative mean Harris hip score of 49.6 ± 7.9 points improved to 91.7 ± 3.0 points at the last follow-up (P < 0.05). The 5-year survival for any reason lead to revision was 96.6%. Five hips were under revision, 1 for acetabular shell loosening and migration, 1 for Vancouver B2 periprosthetic fracture, 1 for fracture of pure alumina liner and 2 for infections. All other prostheses demonstrated no radiographic evidence of loosening. No periprosthetic osteolysis was found. There were 2 cases of dislocations and 2 patients presented postoperatively with "squeaking-like" hips. CONCLUSION: The clinical and radiographic outcomes after primary THA with third-generation ceramic-on-ceramic bearing surfaces are favorable after a minimal follow-up duration of 5 years. The modified alumina-on-alumina bearing implants offer a better option for younger and active patients.

Development of ceramic-on-ceramic implants for total hip arthroplasty.

Over the past three decades, alumina ceramic, now in its third/fourth generation, has been markedly improved in terms of its mechanical properties, including purity, grain microstructure, and burst strength. In the clinic, it is particularly suitable for young and for very active patients. This paper discusses the development and characteristics of different kinds of ceramics. In addition, ceramics in the third/fourth generation which are used in total hip arthroplasty clinically are reviewed in detail.