Osteoporosis and Alzheimer’s disease (AD) are common chronic degenerative disorders which are strongly associated with advanced age. We have previously demonstrated that amyloid beta peptide (Aβ), one of the pathological hallmarks of AD, accumulated abnormally in osteoporotic bone specimens in addition to having an activation effect on osteoclast (Bone 2014,61:164-75). However, the underlying molecular mechanisms remain unclear. Activation of NF-κB, extracellular signal-regulated kinase (ERK) phosphorylates, and calcium oscillation signaling pathways by receptor activator NF-κB ligand (RANKL) plays a pivotal role in osteoclast activation. Targeting this signaling to modulate osteoclast function has been a promising strategy for osteoclast-related diseases. In this study, we investigated the effects of Aβ on RANKL-induced osteoclast signaling pathways in vitro. In mouse bone marrow monocytes (BMMs), Aβ exerted no effect on RANKL-induced osteoclastogenesis but promoted osteoclastic bone resorption. In molecular levels, Aβ enhanced NF-κB activity and IκB-α degradation, activated ERK phosphorylation and stimulated calcium oscillation, thus leading to upregulation of NFAT-c1 expression during osteoclast activation. Taken together, our data demonstrate that Aβ enhances RANKL-induced osteoclast activation through IκB-α degradation, ERK phosphorylation, and calcium oscillation signaling pathways and that Aβ may be a promising agent in the treatment of osteoclast-related disease such as osteoporosis.

Introduction Degenerative lumbar spinal stenosis is a common cause of low back or leg pain and disability in the elderly population. Patients with spinal stenosis who fail to respond to conservative treatment often require surgical interventions. Minimally invasive transforaminal lumbar interbody fusion (TLIF) with microscopic tubular technique (MT-TLIF) is a well-established procedure for lumbar spinal stenosis. Recently, a novel MIS technique, unilateral biportal endoscopic TLIF (UBE-TLIF), has been frequently performed to treat spinal stenosis. However, the efficacy and safety of using UBE-TLIF in this population have not been well examined. Methods and analysis A total of 96 patients with lumbar spinal stenosis will be randomly assigned to the UBE-TLIF group or the MT-TLIF group at a 1:1 ratio to receive UBE-TLIF or MT-TLIF treatment respectively. The primary outcome is the Oswestry Disability Index (ODI) score at 1 year after receiving the surgery. Secondary outcomes include the ODI scores at additional time points, Visual Analogue Scale score, 36-Item Short Form Survey questionnaire, EuroQol 5 Dimensions questionnaire, radiological measurements (disc height, lumbar lordosis angles and vertebral fusion rate) and general condition during hospitalisation. Ethics and dissemination This protocol is approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. All participants of the study will be well informed and written informed consent will be requested. Findings from this trial will be published in peer-reviewed publications, specifically in orthopedic and spinal journals. The completion of this study will not only examine the use of UBE-TLIF in lumbar spinal stenosis but also provide helpful clinical references. Trial registration number ChiCTR2300069333.