Strontium is a widely used anti-osteoporotic agent due to its dual effects on inhibiting bone resorption and stimulating bone formation. Thus, we studied the dose response of strontium on osteo-inductive efficiency in human adipose-derived stem cells (hASCs). Qualitative alkaline phosphatase (ALP) staining, quantitative ALP activity, Alizarin Red staining, real-time polymerase chain reaction and Western blot were used to investigate the in vitro effects of a range of strontium concentrations on hASC osteogenesis and associated signaling pathways. In vitro work revealed that strontium (25–500 μM) promoted osteogenic differentiation of hASCs according to ALP activity, extracellular calcium deposition, and expression of osteogenic genes such as runt-related transcription factor 2, ALP, collagen-1, and osteocalcin. However, osteogenic differentiation of hASCs was significantly inhibited with higher doses of strontium (1000–3000 μM). These latter doses of strontium promoted apoptosis, and phosphorylation of ERK1/2 signaling was increased and accompanied by the downregulation of Bcl-2 and increased phosphorylation of BAX. The inhibition of ERK1/2 decreased apoptosis in hASCs. Lower concentrations of strontium facilitate osteogenic differentiation of hASCs up to a point; higher doses cause apoptosis of hASCs, with activation of the ERK1/2 signaling pathway contributing to this process.
Objective: To estimate the midterm outcome of primary total knee arthroplasty for severe valgus deformity using selective release of tight lateral structures and the least-constrained implant.Methods: We performed total knee arthroplasty on 65 consecutive type II knees with valgus deformity> 20°. Surgery was done via a medial parapatellar approach. Conventional bone cutting was done with selective lateral soft tissue release, and the least-constrained total knee prosthesis possible was used. Posterior stabilized implants were employed in most knees, except for three knees that required the implantation of constrained condylar knee prostheses. The average duration of follow-up lasted for 10.5 years.Results: Preoperatively, average valgus was 30.6°, and average range of motion was 43.7° (range, 0–80°). Postoperatively, average valgus was 7.3° and average range of motion was 110.6° (range, 80–130°). The lateral collateral ligament and iliotibial band were released in all knees, and release of the popliteus tendon was required in two knees. Stable flexion and extension gaps were achieved in most cases, except for two that had medial side instability. Follow-up showed that stability was maintained.Conclusions: This surgical technique combined selective lateral soft tissue release with use of the least-constrained implant possible and was effective for severe valgus deformities of the knee, with good clinical results.