BACKGROUND: Knee joint osteoarthritis is painful and with an overweight of female incidence. The cardinal symptom is pain, which causes compensatory gait changes, and gender differences in pain sensitivity exist. Impact loadings at heel strike during walking are suspected as a co-factor in development of knee osteoarthritis. Thus the purpose of this study was to investigate the influence of experimental muscle pain and gender on generation and attenuation of impact loading during walking.

METHODS: Ten healthy males and 10 healthy females were recruited. Impact loadings during walking were measured using force platforms and accelerometers attached to the tibia and sacrum. Impact ground reaction force peaks and loading rates, and peak accelerations were used to quantify impact loadings. Attenuation was quantified by means of a transfer function between the tibial and sacral accelerometer signals, and the relative peak acceleration reduction. Knee joint kinematics were collected using a three-dimensional movement analysis system. The study was a cross-over study and data were collected before, during, and after experimental vastus medialis pain and a control situation.

FINDINGS: Experimental muscle pain did not affect generation or attenuation of impact loading in either gender. While the impact loading magnitude was similar across genders, lower loading rates and more efficient attenuation were observed in females.

INTERPRETATION: It is concluded that generation and attenuation of impact loadings during walking are independent of quadriceps pain in both genders. The present study does not provide any evidence of the tested variables to address the gender differences in loading rates and attenuation.

Osteoclasts possess a large amount of ion transporters, which participate in bone resorption; of these, the vacuolar-adenosine trisphosphatase (V-ATPase) and the chloride-proton antiporter ClC-7 acidify the resorption lacuna. However, whether other ion transporters participate in this process is currently not well understood. We used a battery of ion channel inhibitors, human osteoclasts, and their subcellular compartments to perform an unbiased analysis of the importance of the different ion transporters for acidification of the resorption lacuna in osteoclasts. CD14(+) monocytes from human peripheral blood were isolated, and mature osteoclasts were generated using RANKL and M-CSF. The human osteoclasts were (1) used for acridine orange assays for evaluation of lysosomal acidification, (2) used for bone resorption assays, (3) used for generation of osteoclasts membranes for acid influx experiments, or (4) lysed in trizol for mRNA isolation for Affymetrix array analysis. Inhibitors targeted toward most of the ion transporters showed low potency in the acidification-based assays, although some inhibitors, such as carbonic anhydrase II and the sodium-hydrogen exchanger (NHE) inhibitors, reduced resorption potently. In contrast, inhibitors targeted at V-ATPase and ClC-7 potently inhibited both acidification and resorption, as expected. We here show evidence that acidification of the resorption lacuna is mainly mediated by V-ATPase and ClC-7. Furthermore, a group of other ion transporters, including carbonic anhydrase II, the NHEs, and potassium-chloride cotransporters, are all involved in resorption but do not seem to directly be involved in acidification of the lysosomes.