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Bone & Joint Research
Vol. 11, Issue 7 | Pages 439 - 452
13 Jul 2022
Sun Q Li G Liu D Xie W Xiao W Li Y Cai M

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain. Cite this article: Bone Joint Res 2022;11(7):439–452


Bone & Joint Open
Vol. 3, Issue 5 | Pages 348 - 358
1 May 2022
Stokes S Drozda M Lee C

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 803 - 813
1 Nov 2022
Guan X Gong X Jiao ZY Cao HY Liu S Lin C Huang X Lan H Ma L Xu B

Aims

The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold.

Methods

Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 137 - 148
1 Apr 2024
Lu Y Ho T Huang C Yeh S Chen S Tsao Y

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

Methods

Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers.


Bone & Joint Research
Vol. 10, Issue 5 | Pages 328 - 339
31 May 2021
Jia X Huang G Wang S Long M Tang X Feng D Zhou Q

Aims

Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

Methods

In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 329 - 330
1 Sep 2005
Jones DG Townshend D Taylor P
Full Access

Introduction and Aims: It has been suggested that elderly patients have poorer outcomes following carpal tunnel decompression than younger patients, especially if there is severe compression. The purpose of this study was to determine the outcomes of carpal tunnel decompression in the elderly patient and whether the outcome could be predicted from pre-operative nerve conduction studies. Method: A retrospective study of all patients over 70 years who had a carpal tunnel release over a three-year period at Dunedin Hospital, with a minimum one-year follow-up. Pre-operative nerve conduction studies were graded from one to six according to severity. Patients were followed up by postal questionnaire (Boston carpal tunnel symptom severity score) and telephone follow-up. Results: 109 procedures were performed in 96 patients. Eight patients had died, two excluded (one with Motor Neurone disease and one acute CTS following fracture) and five were demented and unable to fill out the questionnaire. Eighty-one patients with 92 wrists were available for review. Mean age was 78.6 years. Eighty percent had marked to severe neurophysiological changes (Grade 4–6). Post-operatively, the median Boston score was 1.27 with 84% having a Boston score of < 2.0. Patients were satisfied with the result in 94.6% of procedures. There was a positive correlation between nerve conduction grade and post-operative Boston Score (p=0.042). Conclusion: Despite nerve conduction studies consistent with marked to severe compression, elderly patients have low symptom severity scores following carpal tunnel decompression and a high rate of satisfaction. Carpal tunnel release in patients over 70 years of age is justified and usually associated with a good outcome


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 141 - 141
1 Jul 2002
Freemont A Hoyland J Byers R Bartley C Baird P Jeziorska M Knight M Ross R O’Brien J Sutcliffe J LeMaitre C Goswami A
Full Access

Purpose and Background: We have previously reported our investigations of nerve ingrowth into intervertebral discs (IVD) from patients with mechanical low back pain. We have shown that in discs that are painful on discography (pain level discs) nerves actively grow into the deep annulus fibrosus and nucleus pulposus. Nerve ingrowth accompanies blood vessel ingrowth and advances into the nucleus pulposus from the end plate. The morphology and neurochemistry of these nerves indicate them to be nociceptive. The growth of non-myelinated pain fibres in other settings is regulated by the cytokine Nerve Growth Factor (NGF). In this study, we have investigated the production and distribution of NGF, or more particularly its active isoform – NGF-β, and its receptors, in diseased intervertebral discs in order to establish whether this cytokine might be responsible for the observed nerve ingrowth in this situation. Methods: Tissue sections of 21 pain level, 15 non-pain level diseased and 12 normal intervertebral discs, taken at the time of spinal surgery, and from cadavers, were probed by radioactive in situ hybridisation (ISH) for expression of NGF-β, and by immunohistochemistry (IHC) for its high and low affinity receptors (trk-A and p75 respectively). In addition, either serial sections were stained with cell specific markers (CD31 – endothelial cell, PGP9.5 – neurones, GAP43 – actively growing nerves) or sections were doubled stained (two antibodies or both ISH and IHC). Results: We have demonstrated that NGF-β is synthesised by the endothelial cells of blood vessels growing into the IVD from the end plate. The high affinity receptor is expressed by those small nerve fibres that accompany the vessels and in their offshoots in pain level discs that are growing from perivascular nerves into the disc. In addition to their expressing the nerve specific molecule PGP9.5, the trk-A positive cells also express the nerve growth associated protein GAP43. Conclusion: The data indicate that nerve ingrowth into IVD is regulated by NGF-β. We have localised this production to the endothelial cells of ingrowing blood vessels. NGF-β is a potential therapeutic target for the management of back pain


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 141 - 141
1 Jul 2002
Bucknill A Coward K Plumpton C Tate S Bountra C Birch R Hughes S Anand P
Full Access

Study Design: To examine the innervation of the lumbar spine from patients with lower back pain, and spinal nerve roots from patients with traumatic brachial plexus injuries. Objectives: To demonstrate the presence of nerve fibres in lumbar spine structures and spinal nerve roots, and determine whether they express the sensory neuronespecific sodium channels SNS/PN3 and NaN/SNS2. Summary of background data: The anatomical and molecular basis of low back pain and sciatica is poorly understood. Previous studies have demonstrated sensory nerves in facet joint capsule and prolapsed intervertebral disc, but not in ligamentum flavum. The voltagegated sodium channels SNS/PN3 and NaN/SNS2 are expressed by sensory neurones which mediate pain, but their presence in the lumbar spine is unknown. Methods: Tissue samples (ligamentum flavum n=32; facet joint capsule n=20; intervertebral disc n=15; spinal roots n=8) were immunostained with specific antibodies to protein gene product (PGP) 9.5, a pan-neuronal marker, SNS/PN3 and NaN/SNS2. Results: PGP 9.5-immunoreactive nerve fibres were detected in 72% of ligamentum flavum and 70% of facet joint capsule but only 20% of intervertebral disc specimens. SNS/PN3-and NaN/SNS2-positive fibres were detected in 28% and 3% of ligamentum flavum and 25% and 15% of facet joint capsule specimens respectively. Numerous SNS/PN3 and NaN/SNS2-positive fibres were found in the acutely injured spinal roots, and some were still present in dorsal roots in the chronic state. Conclusions: SNS/PN3 and NaN/SNS2-immunoreactivity is present in a subset of nerve fibres in lumbar spine structures, including ligamentum flavum and injured spinal roots. This is the first time that sensory nerve fibres have been demonstrated in the ligamentum flavum, and this raises the possibility that, contrary to the conclusions of previous studies, this unique ligament may be capable of nociception. Selective SNS/PN3 and NaN/ SNS2 blocking agents may provide new effective therapy for back pain and sciatica, with fewer side effects. Other novel ion channels are being studied in these tissues


Bone & Joint Research
Vol. 10, Issue 8 | Pages 548 - 557
25 Aug 2021
Tao Z Zhou Y Zeng B Yang X Su M

Aims

MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms.

Methods

Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α (TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 (TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 (Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 (CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG.


Bone & Joint Research
Vol. 10, Issue 5 | Pages 307 - 309
3 May 2021
Eitner A Wildemann B


Bone & Joint Open
Vol. 1, Issue 9 | Pages 605 - 611
28 Sep 2020
McKean D Chung SL Fairhead R Bannister O Magliano M Papanikitas J Wong N Hughes R

Aims

To describe the incidence of adverse clinical outcomes related to COVID-19 infection following corticosteroid injections (CSI) during the COVID-19 pandemic. To describe the incidence of positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) testing, positive SARS-COV2 IgG antibody testing or positive imaging findings following CSI at our institution during the COVID-19 pandemic.

Methods

A retrospective observational study was undertaken of consecutive patients who had CSI in our local hospitals between 1 February and 30June 2020. Electronic patient medical records (EPR) and radiology information system (RIS) database were reviewed. SARS-CoV-2 RT-PCR testing, SARS-COV2 IgG antibody testing, radiological investigations, patient management, and clinical outcomes were recorded. Lung findings were categorized according to the British Society of Thoracic Imaging (BSTI) guidelines. Reference was made to the incidence of lab-confirmed COVID-19 cases in our region.


Bone & Joint 360
Vol. 2, Issue 3 | Pages 25 - 27
1 Jun 2013

The June 2013 Wrist & Hand Roundup360 looks at: whether size is a limitation; cancellous bone grafting in scaphoid nonunion; the Kienböck’s dichotomy; late displacement of the distal radius; flexor slide for finger contracture; aesthetic syndactyly; flexor tendon repair; and fixation of trapeziometacarpal cups.


Bone & Joint 360
Vol. 2, Issue 2 | Pages 18 - 20
1 Apr 2013

The April 2013 Wrist & Hand Roundup360 looks at: whether botox is just for Hollywood; supercharging nerve repairs; YouTube research; options for Keinbock’s disease; volar plates; driving and plasters; symptomatic radial malunion; and MRI and acute scaphoid fractures.


Bone & Joint 360
Vol. 1, Issue 3 | Pages 30 - 33
1 Jun 2012

The June 2012 Research Roundup360 looks at: platelet-rich plasma; ageing, bone and mesenchymal stem cells; cytokines and the herniated intervertebral disc; ulcerative colitis, Crohn’s disease and anti-inflammatories; the effect of NSAIDs on bone healing; osteoporosis of the fractured hip; herbal medicine and recovery after acute muscle injury; and ultrasound and the time to fracture union.